Life, death, and the pursuit of apoptosis.
Genes & DevelopmentPublished 1 January 1996Open access
Eileen White
Citations1,319
SJR quartileQ1
SJR score4.00
SNIP1.43
Generate an AI Snapshot to get a quick, structured summary of this paper.
Study Snapshot
ObjectiveStudy objective
MethodsResearch methodology
PopulationPopulation studied
Sample sizeSample sizes
OutcomesStudy outcomes here
ResultsStudy results comes here
LimitationsResearch study limitations comes here
A concise AI-generated summary of the paper will appear here once you click Generate AI Snapshot.
TL;DR
The identification of genes that control cell death and the appreciation of the role of apoptosis in development and disease has been identified and the characterization of the function of these gene products will help to define the process of cell death at the biochemical level.
Keywords
MedicineBiochemistry, Genetics and Molecular Biology
CellWAF1, a potential mediator of p53 tumor suppression
8,356 Citations1993Wafik S. El‐Deiry, Takashi Tokino +8 more
A gene is identified, named WAF1, whose induction was associated with wild-type but not mutant p53 gene expression in a human brain tumor cell line and that could be an important mediator of p53-dependent tumor growth suppression.
Sciencep53 Mutations in Human Cancers
8,110 Citations1991Monica Hollstein, David Sidransky +2 more
Transitions predominate in colorectal carcinomas, brain tumors, leukemias, and lymphomas, whereas G:C to T:A transversions are the most frequent substitutions observed in cancers of the lung and liver.
International review of cytologyCell Death: The Significance of Apoptosis
7,223 Citations1980A H Wyllie, J. F. R. Kerr +1 more
It has proved feasible to categorize most if not all dying cells into one or the other of two discrete and distinctive patterns of morphological change, which have, generally, been found to occur under disparate but individually characteristic circumstances.
CellBcl-2 heterodimerizes in vivo with a conserved homolog, Bax, that accelerates programed cell death
6,013 Citations1993Zoltán N. Oltval, Curt Milliman +1 more
Overexpressed Bax accelerates apoptotic death induced by cytokine deprivation in an IL-3-dependent cell line and counters the death repressor activity of B cl-2, suggesting a model in which the ratio of Bcl-2 to Bax determines survival or death following an apoptotic stimulus.
CellThe p21 Cdk-interacting protein Cip1 is a potent inhibitor of G1 cyclin-dependent kinases
5,667 Citations1993J. Wade Harper
NatureMice deficient for p53 are developmentally normal but susceptible to spontaneous tumours
4,676 Citations1992Lawrence A. Donehower, Michele Harvey +5 more
Observations indicate that a normal p53 gene is dispensable for embryonic development, that its absence predisposes the animal to neoplastic disease, and that an oncogenic mutant form of p53 is not obligatory for the genesis of many types of tumours.
CellTumor suppressor p53 is a direct transcriptional activator of the human bax gene
4,061 Citations1995Toshiyuki Miyashita, John C. Reed
The bax gene promoter region contains four motifs with homology to consensus p53-binding sites and wild-type but not mutant p53 protein bound to oligonucleotides corresponding to this region of the bax promoter, suggesting that bax is a p53 primary-response gene, presumably involved in a p 53-regulated pathway for induction of apoptosis.
ScienceThe Fas Death Factor
4,022 Citations1995Shigekazu Nagata, Pierre Golstein
Fas ligand (FasL), a cell surface molecule belonging to the tumor necrosis factor family, binds to its receptor Fas, thus inducing apoptosis of Fas-bearing cells.
NatureIdentification and inhibition of the ICE/CED-3 protease necessary for mammalian apoptosis
4,011 Citations1995Donald W. Nicholson, Ambereen Ali +14 more
A potent peptide aldehyde inhibitor has been developed and shown to prevent apoptotic events in vitro, suggesting that apopain/CPP32 is important for the initiation of apoptotic cell death.
CellIdentification and characterization of a spinal muscular atrophy-determining gene
3,976 Citations1995Suzie Lefebvre, Lydie Bürglen +14 more
The inverted duplication of a 500 kb element in normal chromosomes is described and the critical region is narrowed to 140 kb within the telomeric region, suggesting that this gene, termed the survival motor neuron (SMN) gene, is an SMA-determining gene.
NatureBcl-2 is an inner mitochondrial membrane protein that blocks programmed cell death
3,786 Citations1990David M. Hockenbery, Gabriel Núñez +3 more
It is demonstrated that Bcl-2 is an integral inner mitochondrial membrane protein of relative molecular mass 25,000 (25k) being localized to mitochondria and interfering with programmed cell death independent of promoting cell division.
CellBcl-2 functions in an antioxidant pathway to prevent apoptosis
3,441 Citations1993David M. Hockenbery, Zoltán N. Oltvai +3 more
A model in which Bcl-2 regulates an antioxidant pathway at sites of free radical generation is proposed in which it protected cells from H2O2- and menadione-induced oxidative deaths and suppressed lipid peroxidation completely.
Naturep21 is a universal inhibitor of cyclin kinases
3,387 Citations1993Yue Xiong, Gregory J. Hannon +4 more
It is found that over expression of p21 inhibits the activity of each member of the cyclin/CDK family, and this results indicate that p21 may be a universal inhibitor of cyclin kinases.
NatureBcl-2 gene promotes haemopoietic cell survival and cooperates with c-myc to immortalize pre-B cells
3,229 Citations1988David L. Vaux, Suzanne Cory +1 more
Results argue that bcl-2 provided a distinct survival signal to the cell and may contribute to neoplasia by allowing a clone to persist until other oncogenes, such as c-myc, become activated.
CellThe mdm-2 oncogene product forms a complex with the p53 protein and inhibits p53-mediated transactivation
3,130 Citations1992Jamil Momand, Gerard P. Zambetti +3 more
A product of the mdm-2 oncogene forms a tight complex with the p53 protein, and the mDM-2oncogene can inhibit p53-mediated transactivation.
Cellbcl-x, a bcl-2-related gene that functions as a dominant regulator of apoptotic cell death
3,113 Citations1993Lawrence Boise, Maribel González‐García +7 more
Data suggest that bcl-x plays an important role in both positive and negative regulation of programmed cell death, as well as in tissues containing long-lived postmitotic cells, such as adult brain.
Cellp53-dependent apoptosis modulates the cytotoxicity of anticancer agents
2,943 Citations1993Scott W. Lowe, H. Earl Ruley +2 more
It is demonstrated that an oncogene, specifically the adenovirus E1A gene, can sensitize fibroblasts to apoptosis induced by ionizing radiation, 5-fluorouracil, etoposide, and adriamycin, and the involvement of p53 in the apoptotic response suggests a mechanism whereby tumor cells can acquire cross-resistance to anticancer agents.
Naturep53 is required for radiation-induced apoptosis in mouse thymocytes
2,890 Citations1993Scott W. Lowe, Earlene M. Schmitt +3 more
It is demonstrated that immature thymocytes lacking p53 die normally when exposed to compounds that may mimic T-cell receptor engagement and to glucocorticoids but are resistant to the lethal effects of ionizing radiation.
NatureSocial controls on cell survival and cell death
2,641 Citations1992Martin Raff
For some mammalian cells, programmed death seems to occur by default unless suppressed by signals from other cells, so dependence on specific survival signals provides a simple way to eliminate misplaced cells, for regulating cell numbers and, perhaps, for selecting the fittest cells.
NatureCleavage of poly(ADP-ribose) polymerase by a proteinase with properties like ICE
2,576 Citations1994Yuri Lazebnik, Scott H. Kaufmann +3 more
A novel protease resembling ICE (prICE) that is active in a cell-free system that reproduces the morphological and biochemical events of apoptosis in the extracts including morphological changes, cleavage of PARP and production of an oligonucleosomal ladder.
NatureA novel heterodimeric cysteine protease is required for interleukin-1βprocessing in monocytes
2,574 Citations1992Nancy A. Thornberry, Herbert G. Bull +27 more
Purification and cloning of the complementary DNA indicates that IL-lβ-converting enzyme is composed of two nonidentical subunits that are derived from a single proenzyme, possibly by autoproteolysis.
CellThe C. elegans cell death gene ced-3 encodes a protein similar to mammalian interleukin-1β-converting enzyme
2,487 Citations1993Yuan Ji
It is proposed that the CED-3 protein acts as a cysteine protease in the initiation of programmed cell death in C. elegans and that cysteINE proteases also function in programmed cell deaths in mammals.
CellFADD, a novel death domain-containing protein, interacts with the death domain of fas and initiates apoptosis
2,424 Citations1995Arul M. Chinnaiyan, Karen O’Rourke +2 more
Findings suggest that FADD may play an important role in the proximal signal transduction of Fas, a mutant of Fas possessing enhanced killing activity, but not the functionally inactive mutants Fas-LPR and Fas-FD8.
CellYama/CPP32β, a mammalian homolog of CED-3, is a CrmA-inhibitable protease that cleaves the death substrate poly(ADP-ribose) polymerase
2,392 Citations1995Muneesh Tewari, Long T. Quan +7 more
It is proposed that Yama may represent an effector component of the mammalian cell death pathway and suggest that CrmA blocks apoptosis by inhibiting Yama.
NatureThymocyte apoptosis induced by p53-dependent and independent pathways
2,292 Citations1993Alan R. Clarke, Colin A. Purdie +5 more
The results show that p53 exerts a significant and dose-dependent effect in the initiation of apoptosis, but only when it is induced by agents that cause DNA-strand breakage.
PubMedTumor suppressor p53 is a regulator of bcl-2 and bax gene expression in vitro and in vivo.
2,165 Citations1994Toshiyuki Miyashita, Stanisław Krajewski +6 more
It is demonstrated that a temperature-sensitive p53 induces temperature-dependent decreases in the expression of the apoptosis-suppressing gene bcl-2 in the murine leukemia cell M1, while simultaneously stimulating increases in theexpression of bax, a gene which encodes a dominant-inhibitor of the Bcl-1 protein.
CellMice Lacking p21CIP1/WAF1 undergo normal development, but are defective in G1 checkpoint control
2,121 Citations1995Chuxia Deng, Pumin Zhang +3 more
The results establish the role of p21CIP1/WAF1 in the G1 checkpoint, but suggest that the anti-apoptotic and theAnti-oncogenic effects of p53 are more complex.
CellBad, a heterodimeric partner for Bcl-xL and Bcl-2, displaces bax and promotes cell death
2,119 Citations1995Elizabeth Yang, Jiping Zha +4 more
A novel interacting protein, Bad, whose homology to Bcl-2 is limited to the BH1 and BH2 domains is identified, whose role in the mammalian cell death pathway is determined by these competing dimerizations in which levels of Bad influence the effectiveness of BCl-2 versus B cl-xL in repressing death.
NatureWild-type p53 induces apoptosis of myeloid leukaemic cells that is inhibited by interleukin-6
2,103 Citations1991Elisheva Yonish-Rouach, Dalia Resnftzky +4 more
CellThe TNF receptor 1-associated protein TRADD signals cell death and NF-κB activation
2,007 Citations1995Hailing Hsu, Jessie Xiong +1 more
The discovery of a novel 34 kDa protein, designated TRADD, that specifically interacts with an intracellular domain of TNFR1 known to be essential for mediating programmed cell death shows that the signaling pathways for TNF-induced cell death and NF-κB activation are distinct.
Nature GeneticsDefinition of a consensus binding site for p53
1,999 Citations1992Wafik S. El‐Deiry, Scott E. Kern +3 more
The results define the DNA sequence elements with which p53 interacts in vitro and which may be important for p53 action in vivo.
NatureEffects of an Rb mutation in the mouse
1,769 Citations1992Tyler Jacks, Amin Fazeli +4 more
A mouse strain has been constructed in which one allele of Rb is disrupted, and heterozygous animals are not predisposed to retinoblastoma, but some display pituitary tumours arising from cells in which the wild-type Rb allele is absent.
ScienceBcl-2 inhibition of neural death: decreased generation of reactive oxygen species
1,677 Citations1993Darci J. Kane, Theodore A. Sarafian +6 more
CellBcl-2-deficient mice demonstrate fulminant lymphoid apoptosis, polycystic kidneys, and hypopigmented hair
1,634 Citations1993Deborah J. Veis, Christine M. Sorenson +2 more
Bcl-2-/-mice complete embryonic development, but display growth retardation and early mortality postnatally, and turn gray with the second hair follicle cycle, implicating a defect in redox-regulated melanin synthesis.
ScienceAltered Cytokine Export and Apoptosis in Mice Deficient in Interleukin-1β Converting Enzyme
1,628 Citations1995Keisuke Kuida, Judith A. Lippke +5 more
Thymocytes from ICE-/- mice were sensitive to apoptosis induced by dexamethasone or ionizing radiation, but were resistant to apoptoses induced by Fas antibody, despite this defect in apoptosis.
ScienceE2F: a Link Between the Rb Tumor Suppressor Protein and Viral Oncoproteins
1,537 Citations1992Joseph R. Nevins
The cellular transcription factor E2F, previously identified as a component of early adenovirus transcription, has been shown to be important in cell proliferation control and appears to be a functional target for the action of the tumor suppressor protein Rb that is encoded by the retinoblastoma susceptibility gene.
NatureSunburn and p53 in the onset of skin cancer
1,511 Citations1994Annemarie Ziegler, Alan S. Jonason +7 more
Skin appears to possess a p53-dependent 'guardian-of-the-tissue' response to DNA damage which aborts precancerous cells, and if this response is reduced in a single cell by a prior p53 mutation, sunburn can select for clonal expansion of the p 53-mutated cell into the AK.
ScienceBax-Deficient Mice with Lymphoid Hyperplasia and Male Germ Cell Death
1,503 Citations1995C. Michael Knudson, Kenneth S. K. Tung +3 more
A Bax knockout mouse was generated that proved viable but displayed lineage-specific aberrations in cell death, and the loss of Bax results in hyperplasia or hypoplasia, depending on the cellular context.
NatureOncoprotein MDM2 conceals the activation domain of tumour suppressor p53
1,464 Citations1993Jonathan D. Oliner, Jennifer A. Pietenpol +4 more
It is shown that, when expressed in Saccharomyces cerevisiae, human MDM2 inhibits human p53's ability to stimulate transcription by binding to a region that nearly coincides with the p53 acidic activation domain.
NatureAssociation between an oncogene and an anti-oncogene: the adenovirus E1A proteins bind to the retinoblastoma gene product
1,434 Citations1988Peter Whyte, Karen Buchkovich +5 more
The interaction between E1A and the retinoblastoma gene product is the first demonstration of a physical link between an oncogene and an anti-oncogene.
CellMice deficient in IL-1β-converting enzyme are defective in production of mature IL-1β and resistant to endotoxic shock
1,415 Citations1995Ping Li, Hamish Allen +15 more
IL-1β-converting enzyme (ICE) plays a dominant role in the generation of mature IL- 1β, a previously unsuspected role in production of IL-1α, but has no autonomous function in apoptosis.
CellInduction of apoptosis in fibroblasts by IL-1β-converting enzyme, a mammalian homolog of the C. elegans cell death gene ced-3
1,375 Citations1993Masahiko Miura
The results suggest that ICE may function during mammalian development to cause programmed cell death.
NatureBH1 and BH2 domains of Bcl-2 are required for inhibition of apoptosis and heterodimerization with Bax
1,329 Citations1994Xiao-Ming Yin, Zoltán N. Oltvai +1 more
Results establish a functional role for the BH1 and BH2 domains and suggest Bcl-2 exerts its action through heterodimerization with Bax, yet still permitted B cl-2 homo-dimerization.
Proceedings of the National Academy of SciencesBCL2 protein is topographically restricted in tissues characterized by apoptotic cell death.
1,280 Citations1991David M. Hockenbery, Mary M. Zutter +3 more
The BCL2 protooncogene encodes an inner mitochondrial membrane protein that blocks programmed cell death and its function as an antidote to apoptosis may confer longevity to progenitor and effector cells in these tissues.
NatureMice deficient for Rb are nonviable and show defects in neurogenesis and haematopoiesis
1,273 Citations1992Eva Y.-H.P. Lee, Chi-Yao Chang +6 more
Transfer of the human retinoblastoma (RB) mini-transgene into the mutant mice corrects the developmental defects and shows that Rb is essential for normal mouse development.
Journal of Biological ChemistryCPP32, a novel human apoptotic protein with homology to Caenorhabditis elegans cell death protein Ced-3 and mammalian interleukin-1 beta-converting enzyme.
1,234 Citations1994Teresa Fernandes‐Alnemri, Gerald Litwack +1 more
The cloned gene encodes a 32-kDa putative cysteine protease (CPP32) with significant homology to Caenorhabditis elegans cell death protein Ced-3, mammalian interleukin-1 beta-converting enzyme (ICE), and the product of the mouse nedd2 gene, which is highly expressed and most abundant in cell lines of lymphocytic origin.
Cellbcl-2-Immunoglobulin transgenic mice demonstrate extended B cell survival and follicular lymphoproliferation
1,222 Citations1989Timothy J. McDonnell, Natasha G. Deane +5 more
CellCloning and structural analysis of cDNAs for bcl-2 and a hybrid bcl-2/immunoglobulin transcript resulting from the t(14;18) translocation
1,222 Citations1986Michael L. Cleary, Stephen D. Smith +1 more
The results suggest that t(14;18) translocations alter expression of the bcl-2 gene both by transcriptional activation and by abnormal posttranscriptional regulation of bCl-2 mRNA.
Cellbcl-2 inhibits multiple forms of apoptosis but not negative selection in thymocytes
1,211 Citations1991Charles L. Sentman, John R. Shutter +3 more
Transgenic mice generated with redirected bcl-2 expression protected immature CD4+8+ thymocytes from glucocorticoid, radiation, and anti-CD3-induced apoptosis and altered T cell maturation, resulting in increased percentages of CD3hi and CD4-8+Thymocytes.
ScienceMassive Cell Death of Immature Hematopoietic Cells and Neurons in Bcl-x-Deficient Mice
1,160 Citations1995Noboru Motoyama, Fanping Wang +9 more
Analyses of bcl-x double-knockout chimeric mice showed that the maturation of B cl-x-deficient lymphocytes was diminished and the life-span of immature lymph cells, but not mature lymphocytes, was shortened.
CellC. elegans cell survival gene ced-9 encodes a functional homolog of the mammalian proto-oncogene bcl-2
1,157 Citations1994Michael O. Hengartner, H. Robert Horvitz
The results suggest that ced-9 and bcl-2 are homologs and that the molecular mechanism of programmed cell death has been conserved from nematodes to mammals.
ScienceGenetic Control of Programmed Cell Death in <i>Drosophila</i>
1,086 Citations1994Kristin White, Megan E. Grether +4 more
A gene, reaper (rpr), that appears to play a central control function for the initiation of programmed cell death (apoptosis) in Drosophila was identified and suggests that the basic cell death program is intact although it was not activated in mutant embryos.
Cellbcl-2 transgene inhibits T cell death and perturbs thymic self-censorship
1,072 Citations1991Andreas Strasser, Alan W. Harris +1 more
It is suggested that modulated bcl-2 expression is a determinant of life and death in normal lymphocytes in mice expressing an E mu-bCl-2 transgene within the T lymphoid compartment.
DevelopmentExpression of baculovirus P35 prevents cell death in <i>Drosophila</i>
1,069 Citations1994Bruce A. Hay, Tanya Wolff +1 more
This work expresses P35 in the developing embryo and eye of the fly Drosophila melanogaster and suggests that one mechanism by which viruses prevent the death of the host cell is to block a cell death pathway that mediates normally occurring cell death.
Journal of VirologyAn apoptosis-inhibiting baculovirus gene with a zinc finger-like motif
1,052 Citations1993N. E. Crook, Rollie J. Clem +1 more
Both iap and p35 were able to block apoptosis induced by actinomycin D, indicating that these genes act by blocking cellular apoptosis rather than by preventing viral stimulation of apoptosis.
NatureRequirement for a functional Rb-1 gene in murine development
1,007 Citations1992Alan R. Clarke, Els Robanus Maandag +6 more
It is reported here that young heterozygous mice do not appear abnormal and do not develop retinoblastoma at a detectable frequency, however, homozygous mutant embryos fail to reach term and show a number of abnormalities in neural and haematopoietic development.
ScienceThe t(14;18) Chromosome Translocations Involved in B-Cell Neoplasms Result from Mistakes in VDJ Joining
1,001 Citations1985Yoshihide Tsujimoto, James D. Gorham +3 more
It is concluded that the t(14;18) chromosome translocation is the result of a mistake during the process of VDJ joining at the pre-B-cell stage of differentiation.
Journal of Biological ChemistryA Novel Protein That Interacts with the Death Domain of Fas/APO1 Contains a Sequence Motif Related to the Death Domain
993 Citations1995Mark Boldin, Eugene Varfolomeev +4 more
Induced expression of the cloned protein results in ligand-independent triggering of cytotoxicity, suggesting that it is involved in cell death induction by Fas/APO1.
CellViral inhibition of inflammation: Cowpox virus encodes an inhibitor of the interleukin-1β converting enzyme
980 Citations1992Caroline A. Ray, Roy A. Black +5 more
Cowpox virus encodes several cytokine response modifiers that act together to inhibit the release of pro-inflammatory cytokines in response to infection, which may contribute significantly to the pathology associated with poxvirus infections.
NatureApoptotic cell death induced by c-myc is inhibited by bcl-2
977 Citations1992Reid P. Bissonnette, Fernando Echeverri +2 more
It is demonstrated that Bcl-2 prevents apoptotic death induced by c-Myc, a mechanism whereby cells can express c- myc without undergoing apoptosis is provided, and a possible explanation for the ability of B cl-2 to synergize with c-myc in cell transformation is given.
CellRIP: A novel protein containing a death domain that interacts with Fas/APO-1 (CD95) in yeast and causes cell death
975 Citations1995Ben Z. Stanger, Philip Leder +3 more
Transient overexpression of RIP causes transfected cells to undergo the morphological changes characteristic of apoptosis, and these properties indicate that RIP is a novel form of apoptotic-inducing protein.
CellThe gene for neuronal apoptosis inhibitory protein is partially deleted in individuals with spinal muscular atrophy
971 Citations1995Natalie Roy, Mani S. Mahadevan +19 more
It is suggested that mutations in the NAIP locus may lead to a failure of a normally occurring inhibition of motor neuron apoptosis resulting in or contributing to the SMA phenotype.
Proceedings of the National Academy of SciencesMCL1, a gene expressed in programmed myeloid cell differentiation, has sequence similarity to BCL2.
968 Citations1993K M Kozopas, Tao Yang +3 more
This report describes a gene, MCL1, that is isolated from the ML-1 human myeloid leukemia cell line during phorbol ester-induced differentiation along the monocyte/macrophage pathway and shows that it has sequence similarity to BCL2, a gene involved in normal lymphoid development and in lymphomas with the t(14;18) chromosome translocation.
NatureExpression of transcription factor E2F1 induces quiescent cells to enter S phase
953 Citations1993D. Gale Johnson, James K. Schwarz +2 more
It is demonstrated that overexpression of the E2F1 complementary DNA can activate DNA synthesis in cells that would otherwise growth-arrest, with an efficiency that is similar to that achieved by the expression of the adenovirus El A gene.
NatureCaenorhabditis elegans gene ced-9 protects cells from programmed cell death
894 Citations1992Michael O. Hengartner, Ronald Ellis +1 more
Cellp53-Dependent apoptosis suppresses tumor growth and progression in vivo
881 Citations1994Holly Symonds, Leonard Krall +5 more
In vivo evidence is provided that p53-dependent apoptosis, occurring in response to oncogenic events, is a critical regulator of tumorigenesis.
Genes & DevelopmentWild-type p53 mediates apoptosis by E1A, which is inhibited by E1B.
877 Citations1993M Debbas, Eileen White
The p53 protein may function as a tumor suppressor by initiating a cell suicide response to deregulation of growth control by E1A, and the E1B 19K and 55K proteins provide separate mechanisms that disable the cell suicide pathway of p53.
NatureProgression from lymphoid hyperplasia to high-grade malignant lymphoma in mice transgenic for the t(14;18)
867 Citations1991Timothy J. McDonnell, Stanley J. Korsmeyer
The transgenic mice provide an animal model for tumour progression in t(14; 18) lymphoma and show that prolonged B-cell life increases tumour incidence, and the long latency, progression from polyclonal to monoclonal disease, and histological conversion are all suggestive of secondary changes.
CellCloning and functional analysis of BAG-1: A novel Bcl-2-binding protein with anti-cell death activity
863 Citations1995Shinichi Takayama, Takaaki Sato +5 more
The findings indicate that bag-1 represents a new type of anti-cell death gene and suggest that some routes of apoptosis induction previously ascribed to Bcl-2-independent pathways may instead reflect a need for the combination of B cl-2 and BAG-1.
Naturep53-Dependent apoptosis in the absence of transcriptional activation of p53-target genes
847 Citations1994Carmé Caelles, Arno Helmberg +1 more
The results indicate that p53 either represses genes necessary for cell survival or is a component of the enzymatic machinery for apoptotic cleav-age or repair of DNA5.
NatureStructure and mechanism of interleukin-lβ converting enzyme
843 Citations1994Keith P. Wilson, Jo-Anne F. Black +9 more
The high-resolution structure of human ICE in complex with an inhibitor has been determined by X-ray diffraction and confirms the relationship between human ICE and cell-death proteins in other organisms.
Proceedings of the National Academy of Sciencesp53 and E2F-1 cooperate to mediate apoptosis.
843 Citations1994Xiangwei Wu, A J Levine
The cell cycle utilizes an interacting or communicative pathway between RB-E2F-1 and p53, a protein partner of the retinoblastoma-susceptibility gene product, RB, which appears to function as a positive regulator or signal for entry into S phase.
CellIch-1, an Ice/ced-3-related gene, encodes both positive and negative regulators of programmed cell death
839 Citations1994Lin Wang, Masayuki Miura +3 more
Overexpression of IchL induces programmed cell death, suggesting that Ich-1 is also a mammalian programmed cellDeath gene, and overexposure of the Ich- 1S suppresses Rat-1 cell death induced by serum deprivation, which suggests that Ich -1 plays an important role in both positive and negative regulation of programmed celldeath in vertebrate animals.
SciencePrevention of Apoptosis by a Baculovirus Gene During Infection of Insect Cells
811 Citations1991Rollie J. Clem, Marcus Fechheimer +1 more
Apoptosis, a morphologically and biochemically defined type of programmed cell death commonly seen in vertebrates, was found to be initiated during baculovirus replication in insect cells and a specific viral gene product, p35, was identified as being responsible for blocking the apoptotic response.
Genes & DevelopmentMice lacking ADPRT and poly(ADP-ribosyl)ation develop normally but are susceptible to skin disease.
779 Citations1995Z Q Wang, B. Auer +5 more
The generation of viableADPRT-/-mice negates an essential role for this enzyme in normal chromatin function, but the impaired proliferation and the onset of skin lesions in older mice suggest a function for ADPRT in response to environmental stress.
NatureCooperative interaction between c-myc and bcl-2 proto-oncogenes
767 Citations1992Abdallah Fanidi, Elizabeth A. Harrington +1 more
It is shown that expression of the bcl-2 protein, B cl-2, specifically abrogates c-mvoinduced apoptosis without affecting the c-myc mitogenic function, providing a novel mechanism for oncogene cooperation, of potential importance both in carcinogenesis and in the evolution of drug resistance in tumours.
Proceedings of the National Academy of SciencesDeregulated transcription factor E2F-1 expression leads to S-phase entry and p53-mediated apoptosis.
763 Citations1994Xu Qin, David M. Livingston +2 more
E2F-1 is a transcription factor suspected of activating genes required for S phase and a known target for the action of RB, the retinoblastoma gene product, which gives rise to proliferative and apoptotic signals.
NatureBcl-2 blocks apoptosis in cells lacking mitochondrial DNA
762 Citations1993Michael D. Jacobson, Julia F. Burne +4 more
It is reported that human mutant cell lines that lack mitochondrial DNA, and therefore do not have a functional respiratory chain, can still be induced to die by apoptosis, and that they can be protected from apoptosis by the overexpression of bcl-2, suggesting that neither apoptosis nor the protective effect of bCl-2 depends on mitochondrial respiration.
ScienceMediation of c-Myc-Induced Apoptosis by p53
750 Citations1994Heiko Hermeking, Dirk Eick
It is suggested that p53 mediates apoptosis as a safeguard mechanism to prevent cell proliferation induced by oncogene activation.
NatureInvolvement of an ICE-like protease in Fas-mediated apoptosis
748 Citations1995Masato Enari, Hubert Hug +1 more
The results suggest an involvement of an ICE-like protease in Fas-mediated apoptosis and TNF-induced cytotoxicity and a specific ICE inhibitor tetrapeptide (acetyl-Tyr-Val-Ala-Asp-chloromethylketone) that also prevents apoptosis induced by anti-Fas antibody.
The EMBO Journalc‐Myc‐induced apoptosis in fibroblasts is inhibited by specific cytokines.
747 Citations1994Elizabeth A. Harrington, Martin R. Bennett +2 more
It is demonstrated that Myc‐induced apoptosis in low serum is inhibited by a restricted group of cytokines, principally the insulin‐like growth factors and PDGF, and Cytokine‐mediated protection from apoptosis is not linked to the cytokines’ abilities to promote growth.
Proceedings of the National Academy of SciencesInactivation of Bcl-2 by phosphorylation.
740 Citations1995Subrata Haldar, Nilamani Jena +1 more
Using the phosphatase inhibitor okadaic acid or the chemotherapeutic drug taxol, it is found that Bcl-2 was phosphorylated in lymphoid cells, which seems to inhibit its ability to interfere with apoptosis.
NatureInduction of apoptosis by the Bcl-2 homologue Bak
734 Citations1995Thomas W. Chittenden, Elizabeth A. Harrington +5 more
The complementary DNA cloning and functional analysis of a new Bcl-2 homologue, Bak, is described, which promotes cell death and counteracts the protection from apoptosis provided by B cl-2.
Molecular and Cellular BiologyWild-Type Human p53 and a Temperature-Sensitive Mutant Induce Fas/APO-1 Expression
734 Citations1995Laurie B. Owen‐Schaub, Wei Zhang +9 more
Temperature-sensitive transcription of Fas/APO-1 occurred in the presence of cycloheximide, indicating that de novo protein synthesis was not required and suggested a direct involvement of p53.
SciencePrevention of Programmed Cell Death of Sympathetic Neurons by the <i>bcl-2</i> Proto-Oncogene
717 Citations1992Irène Garcia, Isabelle Martinou +2 more
Overexpression of the bcl-2 proto-oncogene in cultured sympathetic neurons has now been shown to prevent apoptosis normally induced by deprivation of nerve growth factor, suggesting that the B cl-2 protein may be a major mediator of the effects of neurotrophic factors on neuronal survival.
Genes & DevelopmentThe head involution defective gene of Drosophila melanogaster functions in programmed cell death.
709 Citations1995Megan E. Grether, John Abrams +3 more
The hid gene appears to encode a novel 410-amino-acid protein, and its mRNA is expressed in regions of the embryo where cell death occurs, and can be suppressed completely by expression of the anti-apoptotic p35 protein from baculovirus.
ScienceFAP-1: A Protein Tyrosine Phosphatase That Associates with Fas
687 Citations1995Takaaki Sato, Shinji Irie +2 more
Gene transfer-mediated elevations in FAP-1 partially abolished Fas-induced apoptosis in a T cell line, consistent with an inhibitory effect of Fap-1 on Fas signal transduction.
Genes & DevelopmentStabilization of the p53 tumor suppressor is induced by adenovirus 5 E1A and accompanies apoptosis.
672 Citations1993S. W. Lowe, H. Earl Ruley
The results suggest that the involvement of p53 in tumor suppression and/or apoptosis can be regulated at the level of protein turnover, and a major oncogenic role for E1B is to counter cellular responses to E1A that preclude transformation by E 1A alone.
Proceedings of the National Academy of SciencesThe adenovirus E1A proteins induce apoptosis, which is inhibited by the E1B 19-kDa and Bcl-2 proteins.
665 Citations1992Lakshmi Rao, M Debbas +4 more
E1A-dependent stimulation of cell proliferation is accompanied by apoptosis and thereby insufficient to singly induce transformation, and high-frequency transformation requires a second function encoded by the E1B 19-kDa protein to block apoptosis.
PubMedImmunohistochemical determination of in vivo distribution of Bax, a dominant inhibitor of Bcl-2.
664 Citations1994Stanisław Krajewski, Maryla Krajewska +4 more
In this report, the in vivo patterns of bax gene expression were immunohistochemically assessed in the mouse, with a polyclonal antibody raised against a synthetic peptide corresponding to a unique region in the murine Bax protein.
Genes & DevelopmentSeveral hydrophobic amino acids in the p53 amino-terminal domain are required for transcriptional activation, binding to mdm-2 and the adenovirus 5 E1B 55-kD protein.
652 Citations1994Jiayuh Lin, Jiandong Chen +2 more
It is suggested that 2-4 critical hydrophobic residues in the amino-terminal domain of the p53 protein interact with the transcriptional machinery of the cell resulting in transcriptional activation.
ScienceInhibition of ICE Family Proteases by Baculovirus Antiapoptotic Protein p35
643 Citations1995Nancy J. Bump, Maria Hackett +14 more
NatureProgrammed cell death and Bcl-2 protection in very low oxygen
630 Citations1995Michael D. Jacobson, Martin Raff
It is found that cells cultured in a near-anaerobic atmosphere where the generation of ROS would be expected not to occur, or at least to be greatly reduced, inhibit PCD induced by ROS-generating agents but do not inhibit PCd induced by other means.
SciencePrevention of Programmed Cell Death in <i>Caenorhabditis elegans</i> by Human <i>bcl-2</i>
624 Citations1992David L. Vaux, Irving L. Weissman +1 more
Expression of the human bcl-2 gene in the nematode Caenorhabditis elegans reduced the number of programmed cell deaths, suggesting that the mechanism of programmedcell death controlled by bCl-2 in humans is the same as that in nematodes.
SciencePrevention of Vertebrate Neuronal Death by the <i>crmA</i> Gene
615 Citations1994Valeria Gagliardini, Pierre-Alain Fernandez +5 more
Interleukin-1 beta converting enzyme is a mammalian homolog of CED-3, a protein required for programmed cell death in the nematode Caenorhabditis elegans, and is likely to participate in neuronal death in vertebrates.
NaturePrevention of hypoxia-induced cell death by Bcl-2 and Bcl-xL
614 Citations1995Shigeomi Shimizu, Yutaka Eguchi +4 more
The data suggest that B cl-2 and Bcl-xL exert an anti-cell death function by a mechanism other than regulation of ROS activity.
NatureRequirement of an ICE/CED-3 protease for Fas/APO-1-mediated apoptosis
612 Citations1995Marek Łoś, Marc Van de Craen +8 more
It is reported here that Fas/APO-1-mediated apoptosis requires the activation of a new class of cysteine proteases, including interleukin-lβ-converting enzyme (ICE)8á[euro]-10, which are homologous to the product of the Caenorhabditis elegans cell-death gene ced-3 (refs 11, 12).
Naturep53-dependent apoptosis produced by Rb-deficiency in the developing mouse lens
611 Citations1994Sharon D. Morgenbesser, Bart O. Williams +2 more
The effects of the Rb-deficient state on the development of the ocular lens are described and it is demonstrated that loss of Rb function is associated with unchecked proliferation, impaired expression of differentiation markers, and inappropriate apoptosis in lens fibre cells.
Proceedings of the National Academy of SciencesEpstein-Barr virus-coded BHRF1 protein, a viral homologue of Bcl-2, protects human B cells from programmed cell death.
602 Citations1993S. A. Henderson, David Huen +4 more
By gene transfer, it is shown that BHRF1 resembles Bcl-2 both in its subcellular localization and in its capacity to enhance B-cell survival, suggesting that B HRF1 provides an alternative, B cl-2-independent, means of enhancing B- cell survival that may operate during the virus lytic cycle.
…
