A matter of life and death
Cancer CellPublished 1 February 2002Open access
Douglas R. Green, Gérard I. Evan
Citations1,236
SJR quartileQ1
SJR score19.03
SNIP5.73
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.
Abstract
We propose that deregulation of proliferation, together with a reduction in apoptosis, creates a platform that is both necessary and can be sufficient for cancer. The secondary traits of diverse neoplasms are a consequence of cell proliferation, tissue expansion, and other outcomes of this platform.
Keywords
MedicineHealth ProfessionsBiochemistry, Genetics and Molecular Biology
CellThe Hallmarks of Cancer
28,537 Citations2000Douglas Hanahan, Robert A. Weinberg
This work has been supported by the Department of the Army and the National Institutes of Health, and the author acknowledges the support and encouragement of the National Cancer Institute.
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.
CellAkt Promotes Cell Survival by Phosphorylating and Inhibiting a Forkhead Transcription Factor
6,560 Citations1999Anne Brunet, Azad Bonni +8 more
It is demonstrated that Akt also regulates the activity of FKHRL1, a member of the Forkhead family of transcription factors, which triggers apoptosis most likely by inducing the expression of genes that are critical for cell death, such as the Fas ligand gene.
CellOncogenic ras Provokes Premature Cell Senescence Associated with Accumulation of p53 and p16INK4a
5,054 Citations1997Manuel Serrano, Athena W. Lin +3 more
It is shown that expression of oncogenic ras in primary human or rodent cells results in a permanent G1 arrest, and that the onset of cellular senescence does not simply reflect the accumulation of cell divisions, but can be prematurely activated in response to an onCogenic stimulus.
NatureMolecular characterization of mitochondrial apoptosis-inducing factor
4,050 Citations1999Santos A. Susín, Hans Kristian Lorenzo +14 more
The identification and cloning of an apoptosis-inducing factor, AIF, which is sufficient to induce apoptosis of isolated nuclei is reported, indicating that AIF is a mitochondrial effector of apoptotic cell death.
ScienceProapoptotic BAX and BAK: A Requisite Gateway to Mitochondrial Dysfunction and Death
3,945 Citations2001Michael C. Wei, Wei‐Xing Zong +8 more
CellSmac, a Mitochondrial Protein that Promotes Cytochrome c–Dependent Caspase Activation by Eliminating IAP Inhibition
3,463 Citations2000Chunying Du, Min Fang +3 more
The identification of a novel protein, Smac, which promotes caspase activation in the cytochrome c/Apaf-1/caspase-9 pathway and increases cells' sensitivity to apoptotic stimuli is reported.
NatureProliferation, cell cycle and apoptosis in cancer
3,400 Citations2001Gérard I. Evan, Karen H. Vousden
Deregulated cell proliferation provides a minimal 'platform' necessary to support further neoplastic progression and should be targeted withroit targeting to have potent and specific therapeutic consequences.
NatureA caspase-activated DNase that degrades DNA during apoptosis, and its inhibitor ICAD
3,182 Citations1998Masato Enari, Hideki Sakahira +4 more
A caspase-activated deoxyribonuclease (CAD) and its inhibitor (ICAD) have now been identified in the cytoplasmic fraction of mouse lymphoma cells and seems to function as a chaperone for CAD during its synthesis, remaining complexed with CAD to inhibit its DNase activity.
CellApaf-1, a Human Protein Homologous to C. elegans CED-4, Participates in Cytochrome c–Dependent Activation of Caspase-3
3,146 Citations1997Hua Zou, William J. Henzel +3 more
The purification and cDNA cloning of Apaf-1, a novel 130 kd protein from HeLa cell cytosol that participates in the cytochrome c-dependent activation of caspase-3, leading to apoptosis is reported here.
CellInduction of apoptosis in fibroblasts by c-myc protein
2,970 Citations1992Gérard I. Evan, Andrew H. Wyllie +7 more
It is demonstrated that deregulated c-myc expression induces apoptosis in cells growth arrested by a variety of means and at various points in the cell cycle.
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.
CellSerine Phosphorylation of Death Agonist BAD in Response to Survival Factor Results in Binding to 14-3-3 Not BCL-XL
2,622 Citations1996Jiping Zha, Hisashi Harada +3 more
The rapid phosphorylation of BAD following IL-3 connects a proximal survival signal with the BCL-2 family, modulating this checkpoint for apoptosis and enhanced BAD's death-promoting activity.
Annual Review of Cell and Developmental BiologyBiochemical Pathways of Caspase Activation During Apoptosis
2,585 Citations1999I. Imawati Budihardjo, Holt Oliver +3 more
This review focuses on the two most well-studied pathways of caspase activation: the cell surface death receptor pathway and the mitochondria-initiated pathway.
CellIdentification of DIABLO, a Mammalian Protein that Promotes Apoptosis by Binding to and Antagonizing IAP Proteins
2,339 Citations2000Anne M. Verhagen, Paul G. Ekert +7 more
DIABLO (direct IAP binding protein with low pI) is a novel protein that can bind MIHA and can also interact with MIHB and MIHC and the baculoviral IAP, OpIAP.
Molecular CellPUMA, a Novel Proapoptotic Gene, Is Induced by p53
2,291 Citations2001Katsunori Nakano, Karen H. Vousden
A novel gene named PUMA (p53 upregulated modulator of apoptosis) is identified as a target for activation by p53, and PUMA is likely to play a role in mediating p53-induced cell death through the cytochrome c/Apaf-1-dependent pathway.
ScienceNoxa, a BH3-Only Member of the Bcl-2 Family and Candidate Mediator of p53-Induced Apoptosis
2,086 Citations2000Eri Oda, Rieko Ohki +7 more
A previously unidentified pro-apoptotic gene, Noxa, which encodes a Bcl-2 homology 3 (BH3)-only member of the BCl-2 family of proteins may represent a mediator of p53-dependent apoptosis.
Proceedings of the National Academy of SciencesNew insights into tumor suppression: PTEN suppresses tumor formation by restraining the phosphoinositide 3-kinase/AKT pathway
2,025 Citations1999Lewis C. Cantley, Benjamin G. Neel
A series of publications over the past year now suggest a mechanism by which PTEN loss of function results in tumors, and PTEN appears to negatively control the phosphoinositide 3-kinase signaling pathway for regulation of cell growth and survival by dephosphorylating the 3 position ofosphoinositides.
NatureEndonuclease G is an apoptotic DNase when released from mitochondria
1,735 Citations2001Lily Y. Li, Xu Luo +1 more
The identification and characterization of another nuclease that is specifically activated by apoptotic stimuli and is able to induce nucleosomal fragmentation of DNA in fibroblast cells from embryonic mice lacking DFF is reported.
Molecular CellBCL-2, BCL-XL Sequester BH3 Domain-Only Molecules Preventing BAX- and BAK-Mediated Mitochondrial Apoptosis
1,692 Citations2001Emily H. Cheng, Michael C. Wei +5 more
In mammals, BH3 domain-only molecules activate multidomain proapoptotic members to trigger a mitochondrial pathway, which both releases cytochrome c to activate caspases and initiates caspase-independent mitochondrial dysfunction.
ScienceA Matter of Life and Cell Death
1,511 Citations1998Gérard I. Evan, Trevor D. Littlewood
In multicellular organisms, mutations in somatic cells affecting critical genes that regulate cell proliferation and survival cause fatal cancers, and there exist potent mechanisms that limit the expansion of affected cells by suppressing their proliferation or triggering their suicide.
Molecular CellThe Combined Functions of Proapoptotic Bcl-2 Family Members Bak and Bax Are Essential for Normal Development of Multiple Tissues
1,474 Citations2000Tullia Lindsten, Andrea J. Ross +19 more
Bax and Bak have overlapping roles in the regulation of apoptosis during mammalian development and tissue homeostasis and are found to be developmentally normal and reproductively fit.
Nature Cell BiologyMembrane blebbing during apoptosis results from caspase-mediated activation of ROCK I
1,287 Citations2001Mathew L. Coleman, Erik Sahai +4 more
It is shown that the Rho effector protein ROCK I, which contributes to phosphorylation of myosin light-chains, myOSin ATPase activity and coupling of actin–myosin filaments to the plasma membrane, is cleaved during apoptosis to generate a truncated active form.
Molecular CellPUMA Induces the Rapid Apoptosis of Colorectal Cancer Cells
1,280 Citations2001Jian Yu, Lin Zhang +3 more
ScienceCaspase-3-Generated Fragment of Gelsolin: Effector of Morphological Change in Apoptosis
1,235 Citations1997Srinivas Kothakota, Toshifumi Azuma +9 more
Neutrophils isolated from mice lacking gelsolin had delayed onset of both blebbing and DNA fragmentation, following apoptosis induction, compared with wild-type neutrophils, indicating one physiological effector of morphologic change during apoptosis.
Proceedings of the National Academy of SciencesA phosphatidylinositol 3-kinase/Akt pathway promotes translocation of Mdm2 from the cytoplasm to the nucleus
1,209 Citations2001Lindsey D. Mayo, David B. Donner
The demonstration that PI3-kinase/Akt signaling affects Mdm2 localization provides insight into how this pathway, which is inappropriately activated in many malignancies, affects the function of p53.
Current Opinion in Cell BiologyAnoikis mechanisms
1,199 Citations2001Steven M. Frisch, Robert A. Screaton
Anoikis is defined as apoptosis that is induced by inadequate or inappropriate cell-matrix interactions and the initiation of the caspase cascade remains to be explained.
Molecular and Cellular BiologyBid Induces the Oligomerization and Insertion of Bax into the Outer Mitochondrial Membrane
1,194 Citations2000Robert Eskes, Solange Desagher +2 more
It is shown that following binding to the BH3-domain-only proapoptotic protein Bid, Bax oligomerizes and then integrates in the outer mitochondrial membrane, where it triggers cytochromec release and may represent a key step in pathways leading to apoptosis.
NatureSuppression of c-Myc-induced apoptosis by Ras signalling through PI(3)K and PKB
1,160 Citations1997Andrea Kauffmann-Zeh, Pablo Rodriguez‐Viciana +5 more
It is shown that Ras activation of PI(3)K suppresses c-Myc-induced apoptosis through the activation of PKB/Akt but not p70S6K, and that Ras is an effective promoter of apoptosis, through the Raf pathway, which activates contradictory intracellular pathways that modulate cell viability.
Molecular CellA Serine Protease, HtrA2, Is Released from the Mitochondria and Interacts with XIAP, Inducing Cell Death
1,099 Citations2001Yasuyuki Suzuki, Yuzuru Imai +4 more
HtrA2 is a Smac-like inhibitor of IAP activity with a serine protease-dependent cell death-inducing activity, which is neither accompanied by a significant increase in caspase activity nor inhibited by casp enzyme inhibitors, including XIAP.
Nature Cell BiologyThe coordinate release of cytochrome c during apoptosis is rapid, complete and kinetically invariant
1,059 Citations2000Joshua C. Goldstein, Nigel J. Waterhouse +3 more
It is found that the electron-transport chain can maintain the mitochondrial transmembrane potential even after cytochrome c has been released, and the addition of caspase inhibitors does not change the duration of release.
Molecular CellThe Proapoptotic Activity of the Bcl-2 Family Member Bim Is Regulated by Interaction with the Dynein Motor Complex
1,038 Citations1999Hamsa Puthalakath, David C.S. Huang +3 more
The regulation of the proapoptotic activity of the BH3-only protein Bim was examined and it was found that certain apoptotic stimuli disrupted the interaction between LC8 and the dynein motor complex and therefore constitutes an initiating event in apoptosis signaling.
Nature Reviews Molecular Cell BiologyThe mitochondrion in apoptosis: how Pandora's box opens
1,017 Citations2001Naoufal Zamzami, Guido Kroemer
It is suggested that opening of a multiprotein complex called the mitochondrial permeability transition pore complex is sufficient (and, usually, necessary) for triggering apoptosis.
Nature Reviews Molecular Cell BiologyThe INK4a/ARF network in tumour suppression
974 Citations2001Charles J. Sherr
A complex signalling network that interconnects the activities of RB and p53 monitors oncogenic stimuli to provide a cell-autonomous mode of tumour surveillance.
NatureInactivation of the apoptosis effector Apaf-1 in malignant melanoma
959 Citations2001Marı́a S. Soengas, Paola Capodieci +10 more
It is concluded that Apaf-1 is inactivated in metastatic melanomas, which leads to defects in the execution of apoptotic cell death, which may contribute to the low frequency of p53 mutations observed in this highly chemoresistant tumour type.
Genes & DevelopmentInhibition of early apoptotic events by Akt/PKB is dependent on the first committed step of glycolysis and mitochondrial hexokinase
948 Citations2001Kathrin Gottlob, Nathan Majewski +4 more
It is proposed that Akt increases coupling of glucose metabolism to oxidative phosphorylation and regulates PT pore opening via the promotion of hexokinase-VDAC interaction at the outer mitochondrial membrane.
Nature Reviews Molecular Cell BiologyBreaking the mitochondrial barrier
940 Citations2001Jean‐Claude Martinou, Douglas R. Green
Pro- and anti-apoptotic members of the Bcl-2 family control the permeability of the outer mitochondrial membrane by forming autonomous pores in the membrane or by collaborating with components of the permeable transition pore.
Proceedings of the National Academy of SciencesAKT plays a central role in tumorigenesis
940 Citations2001Joseph R. Testa, Alfonso Bellacosa
This issue of PNAS, Mayo and Donner report on yet another function of AKT, involving regulation of the Mdm2/p53 pathway, and define a family of closely related, highly conserved cellular homologues.
Molecular CellThree-Dimensional Structure of the Apoptosome
895 Citations2002Devrim Acehan, Xuejun Jiang +4 more
Molecular modeling was used to identify the caspase recruitment and WD40 domains within the apoptosome and to infer likely positions of the CED4 homology motif and cytochrome c, suggesting a plausible role for cy tochrome c in apoptosomes assembly.
Nature Cell BiologyCaspase-3-mediated cleavage of ROCK I induces MLC phosphorylation and apoptotic membrane blebbing
889 Citations2001Michaël Sebbagh, Claire Renvoizé +4 more
Activation of ROCK I by caspase-3 seems to be responsible for bleb formation in apoptotic cells.
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.
PubMedConstitutive c-myc expression in an IL-3-dependent myeloid cell line suppresses cell cycle arrest and accelerates apoptosis.
870 Citations1991David S. Askew, Richard A. Ashmun +2 more
The premature induction of apoptosis in cells harboring a deregulated c-myc gene suggests that apoptosis may be an important mechanism in the elimination of hematopoietic cells Harboring mutations, such as constitutive c- myc expression, which imbalance normal cell cycle regulatory controls.
ScienceMembrane and Morphological Changes in Apoptotic Cells Regulated by Caspase-Mediated Activation of PAK2
748 Citations1997Thomas Rudel, Gary Bokoch
Proteolytic activation of PAK2 represents a guanosine triphosphatase-independent mechanism ofPAK regulation that allows PAK 2 to regulate morphological changes that are seen in apoptotic cells.
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.
NatureRole of NF-κB in p53-mediated programmed cell death
740 Citations2000Kevin M. Ryan, Mary K. Ernst +2 more
It is concluded that inhibition of NF-κB in tumours that retain wild-type p53 may diminish, rather than augment, a therapeutic response.
Journal of Biological ChemistryIdentification of Omi/HtrA2 as a Mitochondrial Apoptotic Serine Protease That Disrupts Inhibitor of Apoptosis Protein-Caspase Interaction
732 Citations2002R.P. Hegde, Srinivasa M. Srinivasula +9 more
The results provide clear evidence for the involvement of a mitochondrial serine protease in the apoptotic pathway, emphasizing the critical role of the mitochondria in cell death.
ScienceRole for c-myc in Activation-Induced Apoptotic Cell Death in T Cell Hybridomas
699 Citations1992Yufang Shi, Jacqueline M. Glynn +4 more
Antisense oligonucleotides corresponding to c-myc block the constitutive expression of c-Myc protein in T cell hybridomas and interfere with all aspects of activation-induced apoptosis without affecting lymphokine production in these cells.
ScienceBmf: A Proapoptotic BH3-Only Protein Regulated by Interaction with the Myosin V Actin Motor Complex, Activated by Anoikis
663 Citations2001Hamsa Puthalakath, Andreas Villunger +6 more
At least two mammalian BH3-only proteins, Bmf and Bim, function to sense intracellular damage by their localization to distinct cytoskeletal structures.
ScienceApaf-1 and Caspase-9 in p53-Dependent Apoptosis and Tumor Inhibition
663 Citations1999Marı́a S. Soengas, Rodolfo Alarcón +6 more
Mouse embryo fibroblast cells deficient in Apaf-1 and caspase-9, and expressing c-Myc, were resistant to apoptotic stimuli that mimic conditions in developing tumors.
Nature Cell BiologyBcl-2 proteins: regulators of apoptosis or of mitochondrial homeostasis?
660 Citations1999Matthew G. Vander Heiden, Craig B. Thompson
The current understanding of the part played by mitochondria in apoptosis is synthesized with a consideration of how Bcl-2 proteins might control cell death through an ability to regulate mitochondrial physiology.
Journal of Biological ChemistryLysosomal Protease Pathways to Apoptosis
656 Citations2001Veronika Stoka, Boris Turk +14 more
Data suggest that Bid represents a sensor that allows cells to initiate apoptosis in response to widespread adventitious proteolysis, supported by the finding that cytosolic extracts from mice ablated in the bid gene are impaired in the ability to release cytochrome c in Response to lysosome extracts.
Proceedings of the National Academy of SciencesUbiquitin-protein ligase activity of X-linked inhibitor of apoptosis protein promotes proteasomal degradation of caspase-3 and enhances its anti-apoptotic effect in Fas-induced cell death
648 Citations2001Yasuyuki Suzuki, Yui Nakabayashi +1 more
It is demonstrated that the ubiquitin-protein ligase activity of XIAP promotes the degradation of caspase-3, which enhances its anti-apoptotic effect.
Journal of Biological ChemistryLoss of Phospholipid Asymmetry and Surface Exposure of Phosphatidylserine Is Required for Phagocytosis of Apoptotic Cells by Macrophages and Fibroblasts
637 Citations2001Valerie A. Fadok, Aimee de Cathelineau +3 more
Observations directly demonstrate that loss of phospholipid asymmetry and PS expression is required for phagocyte engulfment of apoptotic cells and imply a critical, if not obligatory, role for PS recognition in the uptake process.
Nature Cell BiologyApaf-1 is a transcriptional target for E2F and p53
587 Citations2001Maria Cristina Moroni, Emma Hickman +6 more
It is shown that E2F1 directly regulates the expression of Apaf-1, the gene for apoptosis protease-activating factor 1, which provides a direct link between the deregulation of the pRB pathway and apoptosis.
Journal of Biological ChemistryHtrA2 Promotes Cell Death through Its Serine Protease Activity and Its Ability to Antagonize Inhibitor of Apoptosis Proteins
549 Citations2002Anne M. Verhagen, John Silke +11 more
The Journal of Cell BiologyInhibition of Ced-3/ICE-related Proteases Does Not Prevent Cell Death Induced by Oncogenes, DNA Damage, or the Bcl-2 Homologue Bak
547 Citations1997Nicola McCarthy, Moira K. B. Whyte +2 more
The data indicate that IRPs constitute part of the execution machinery of mammalian apoptosis induced by deregulated oncogenes, DNA damage, or Bak but that they act after the point at which cells become committed to apoptosis or can be rescued by survival factors.
Journal of Biological ChemistryCaspase-9 Can Be Activated without Proteolytic Processing
497 Citations1999Henning R. Stennicke, Quinn L. Deveraux +4 more
The recombinant form of the proapoptotic caspase-9 purified following expression in Escherichia coliis processed at Asp315, but largely inactive; however, when added to cytosolic extracts of human 293 cells it is activated 2000-fold in the presence of cytochrome c and dATP.
Molecular CellReversible Activation of c-Myc in Skin
467 Citations1999Stella Pelengaris, Trevor D. Littlewood +3 more
It is shown that activation of c-MycER in adult suprabasal epidermis rapidly triggers proliferation and disrupts differentiation of postmitotic keratinocytes, changes that resemble hyperplastic actinic keratosis, a commonly observed human precancerous epithelial lesion.
The Journal of Cell BiologyCytochrome C Maintains Mitochondrial Transmembrane Potential and Atp Generation after Outer Mitochondrial Membrane Permeabilization during the Apoptotic Process
447 Citations2001Nigel J. Waterhouse, Joshua C. Goldstein +4 more
It is found that when caspase activity is inhibited, mitochondrial outer membrane permeabilization causes a rapid depolarization of mitochondrial transmembrane potential, which recovers to original levels over the next 30–60 min and is then maintained.
Trends in Cell BiologyStress management – heat shock protein-70 and the regulation of apoptosis
437 Citations2001Helen M. Beere
The functional interactions between the stress response and the apoptotic cell death pathway are discussed and how these might impact on determining cellular survival are discussed.
CellDominant negative MYC blocks transformation by ABL oncogenes
407 Citations1992Charles L. Sawyers, Wendy Callahan +1 more
It is demonstrated that dominant negative MYC suppressed transformation of primary mouse bone marrow pre-B cells by BCR-ABL and demonstrated that c-MYC is essential for transformation and help define the pathway by which these proteins cause transformation.
PubMedAn informatics approach identifying markers of chemosensitivity in human cancer cell lines.
399 Citations2000Sally A. Amundson, Timothy G. Myers +4 more
The Journal of Experimental MedicineEarly Activation of Caspases during T Lymphocyte Stimulation Results in Selective Substrate Cleavage in Nonapoptotic Cells
386 Citations1999Antoine Alam, Luchino Y. Cohen +2 more
It is shown that the caspase inhibitor benzyloxycarbonyl (Cbz)-Val-Ala-Asp(OMe)-fluoromethylketone (zVAD) blocks proliferation, major histocompatibility complex class II expression, and blastic transformation during stimulation of peripheral blood lymphocytes.
CellStructure and polymorphism of human telomere-associated DNA
385 Citations1990William R. Brown, Philip J. MacKinnon +4 more
Analysis of DNA sequences associated with four different human telomeres identifies a new source of human genetic variation and indicates that the canonical features of the organization of telomere-associated DNA are widely conserved in evolution.
ScienceRequirement for the CD95 Receptor-Ligand Pathway in c-Myc-Induced Apoptosis
369 Citations1997Anne‐Odile Hueber, Martin Zörnig +4 more
The Journal of Cell BiologyEssential Role of Voltage-Dependent Anion Channel in Various Forms of Apoptosis in Mammalian Cells
363 Citations2001Shigeomi Shimizu, Yosuke Matsuoka +3 more
Evidence is provided that the VDAC plays an essential role in apoptogenic cytochrome c release and apoptosis in mammalian cells.
PubMedp53-dependent and -independent regulation of the death receptor KILLER/DR5 gene expression in response to genotoxic stress and tumor necrosis factor alpha.
363 Citations1998M. Saeed Sheikh, Timothy F. Burns +6 more
It is demonstrated that the DR KILLER/DR5 gene is regulated in a p53-dependent and -independent manner during genotoxic and nongenotoxic stress-induced apoptosis and that its induction by TNF-alpha, p53, or DNA damage is not the consequence of apoptosis induced by these agents.
The EMBO JournalThe anti‐apoptosis function of Bcl‐2 can be genetically separated from its inhibitory effect on cell cycle entry
336 Citations1997David C.S. Huang, Lorraine A. O’Reilly +2 more
Observations provide evidence that the anti‐apoptotic function of Bcl‐2 is mechanistically distinct from its inhibitory influence on cell cycle entry.
Genes & Developmentc-Myc-induced sensitization to apoptosis is mediated through cytochrome c release
334 Citations1999Philippe Juin, Anne‐Odile Hueber +2 more
It is concluded that c-Myc promotes apoptosis by causing the release of cytochrome c, but the ability of cy tochrome c to activate apoptosis is critically dependent upon other signals.
Proceedings of the National Academy of SciencesCross talk between cell death and cell cycle progression: BCL-2 regulates NFAT-mediated activation.
334 Citations1996Gerald P. Linette, Y Li +2 more
Select genetic aberrations in the apoptotic pathway reveal a cell autonomous coregulation of activation, as well as a cysteine protease inhibitor that also blocks apoptosis.
Journal of Biological ChemistryRegulation of GLUT1 Gene Transcription by the Serine/Threonine Kinase Akt1
328 Citations1999Andreas Barthel, Steven T. Okino +5 more
The findings imply that theGLUT1 gene responds to insulin at the transcriptional level and that Akt mediates a step in the activation of GLUT1gene expression in this system.
Nature MedicineInduction of apoptosis in chronic myelogenous leukemia cells through nuclear entrapment of BCR–ABL tyrosine kinase
328 Citations2001Paolo Vigneri, Jean Y. J. Wang
Nuclear entrapment of BCR–ABL can be used as a therapeutic strategy to selectively kill chronic myelogenous leukemia cells, and the combined treatment with STI571 and LMB causes the irreversible and complete killing of B CR-ABL transformed cells, whereas the effect of either drug alone is fully reversible.
Blood Cells Molecules and DiseasesInhibition of the ABL Kinase Activity Blocks the Proliferation of BCR/ABL+Leukemic Cells and Induces Apoptosis
319 Citations1997Carlo Gambacorti‐Passerini, Philipp le Coutre +10 more
The activity of CGP57148B on the spontaneous proliferation of both fresh and cultured, leukemic and normal, BCR/ABL positive and negative cells, and its mechanism of action are investigated to support the use of this molecule in initial clinical studies.
Proceedings of the National Academy of SciencesSelective killing of transformed cells by cyclin/cyclin-dependent kinase 2 antagonists
319 Citations1999Ying-Nan P. Chen, Sushil Sharma +7 more
It is reported that cell membrane-permeable forms of such peptides preferentially induced transformed cells to undergo apoptosis relative to nontransformed cells, suggesting that deregulation of E2F and inhibition ofcdk2 are synthetically lethal and provide a rationale for the development of cdk2 antagonists as antineoplastic agents.
Experimental Cell ResearchRegulation of p53 Function
316 Citations2001Douglas Woods, Karen H. Vousden
The Journal of Cell BiologyThe Release of Cytochrome c from Mitochondria during Apoptosis of NGF-deprived Sympathetic Neurons Is a Reversible Event
305 Citations1999Isabelle Martinou, Solange Desagher +5 more
Data suggest that depletion of cytochrome c from mitochondria is a controlled process compatible with function recovery, and the ability of sympathetic neurons to recover fully from trophic factor deprivation provided irreversible caspase inhibitors have been present during the insult period, has therapeutical implications for a number of acute neuropathologies.
Journal of Biological ChemistryAkt and Bcl-xL Promote Growth Factor-independent Survival through Distinct Effects on Mitochondrial Physiology
302 Citations2001David R. Plas, Sunit Talapatra +3 more
A comparison of Akt- and Bcl-xL-dependent cell survival was undertaken using interleukin-3-dependent FL5.12 cells, and it is shown that Akt and B cl-x L suppress mitochondrion-initiated apoptosis by distinct mechanisms.
Current Opinion in Genetics & DevelopmentOncogenes and cell death
265 Citations1994Elizabeth A. Harrington, Abdallah Fanidi +1 more
Paradigms in the cell death pathway suggest the pathways of cell proliferation and cell death may be tightly coupled, an idea that may have dramatic implications for models of oncogene co-operation and carcinogenesis.
Genes & DevelopmentCooperating oncogenes converge to regulate cyclin/cdk complexes.
226 Citations1997Alison C. Lloyd, F Obermüller +4 more
Signaling by Raf and its cooperating partners converges at the regulation of cyclin/cdk complexes, with the cellular responses to Raf modulated by p53.
Pharmacology & TherapeuticsDeath the Fas way: regulation and pathophysiology of CD95 and its ligand
199 Citations2000Kamal Kant Sharma, R.X Wang +9 more
The mechanisms that regulate Fas and FasL expression are focused on, and how their deregulation leads to diseases are reviewed.
Journal of Biological ChemistryGranzyme B-mediated Apoptosis Proceeds Predominantly through a Bcl-2-inhibitable Mitochondrial Pathway
190 Citations2001Michael J. Pinkoski, Nigel J. Waterhouse +7 more
Time lapse confocal microscopy is used to demonstrate that mitochondrial cytochromec release is the primary mode of granzyme B-induced apoptosis and that Bcl-2 is a potent inhibitor of this pivotal event.
The Journal of Cell BiologyCaspase Inhibition Extends the Commitment to Neuronal Death Beyond Cytochrome <i>c</i> Release to the Point of Mitochondrial Depolarization
185 Citations2000Mohanish Deshmukh, Keisuke Kuida +1 more
Caspase inhibition extended commitment to death in trophic factor–deprived sympathetic neurons and allowed recovery of neurons arrested after the loss of cytochrome c, but not beyond the subsequent loss of mitochondrial membrane potential.
Cell Death and DifferentiationAnti-apoptotic oncogenes prevent caspase-dependent and independent commitment for cell death
180 Citations1998Gustavo P. Amarante‐Mendes, Deborah Finucane +4 more
Oncogenesis is promoted not by simply interfering with caspase-mediated apoptosis, but by preventing an upstream event which is defined as the commitment point for cell death.
Proceedings of the National Academy of SciencesOncogene-dependent apoptosis is mediated by caspase-9
172 Citations1998Howard O. Fearnhead, Joe Rodriguez +5 more
As predicted by the in vitro system, preventing caspase-9 activation blocked drug-induced apoptosis in cells sensitized by E1A, an adenoviral oncogene.
Journal of Biological ChemistryNFκB Mediates Apoptosis through Transcriptional Activation of Fas (CD95) in Adenoviral Hepatitis
163 Citations2000Florian Kühnel, Lars Zender +5 more
Journal of Biological ChemistryPhosphoinositide 3-OH Kinase (PI3K) and PKB/Akt Delay the Onset of p53-mediated, Transcriptionally Dependent Apoptosis
140 Citations1999Peter Sabbatini, Frank McCormick
It is demonstrated in this report that constitutively active PI3K and PKB/Akt are capable of significantly delaying the onset of p53-mediated apoptosis, providing the first direct and unambiguous link between p 53- mediated apoptosis and thePI3K-PKB-Akt signaling pathway.
OncogeneModulation of cellular apoptotic potential: contributions to oncogenesis
125 Citations1999Vuk Stambolic, Tak W. Mak +1 more
This review focuses on the regulation and mechanisms by which PKB activation protects cells and the oncologic consequences of dysregulation of the pathway.
Journal of Biological ChemistryDefective Cytochrome c-dependent Caspase Activation in Ovarian Cancer Cell Lines due to Diminished or Absent Apoptotic Protease Activating Factor-1 Activity
124 Citations2001Beni B. Wolf, Martin Schüler +7 more
Regulation of APAF-1 activity may be important for apoptosis regulation in some ovarian cancers because it correlated in some but not all cell lines with resistance to apoptosis.
PubMedModulation of c-Myc activity and apoptosis in vivo.
87 Citations1996Rodolfo Alarcón, Brent Rupnow +3 more
It is proposed that the ability of activated c-Myc to enhance cellular proliferation might contribute to the genesis of early neoplasms that are held in check by the alternate ability of c- myc to induce apoptosis of cells that have outgrown their supply of oxygen or other factors associated with hypoxic regions of solid tumors.
The Journal of ImmunologyAdenovirus E1A Oncogene Expression in Tumor Cells Enhances Killing by TNF-Related Apoptosis-Inducing Ligand (TRAIL)
68 Citations2000John M. Routes, Sharon Ryan +5 more
Current Opinion in OncologyAntisense therapeutics: lessons from early clinical trials
61 Citations2001Keith T. Flaherty, James Stevenson +1 more
The authors review the early clinical experience with antisense oligodeoxynucleotides, documenting their limited toxicity profile and initial reports of efficacy, and suggest that antisense therapy alone appears capable of limiting disease progression in some patients, but major tumor responses are uncommon.
Current BiologyA ‘non-canonical’ DNA-binding element mediates the response of the Fas-ligand promoter to c-Myc
50 Citations2000Shailaja Kasibhatla, Helen M. Beere +3 more
A precise physiological role is identified in the induction of apoptosis as a transcriptional regulator of the FasL gene through a non-canonical binding site for c-Myc-Max heterodimers in the Fas L promoter.
The Journal of ImmunologyDissociation of cytokine signals for proliferation and apoptosis
30 Citations1997Yufang Shi, R Wang +5 more
It is demonstrated that BAF-B03 cells transfected with the wild-type IL-2R beta-chain undergo apoptosis when stimulated with IL- 2 or IL-3 in the absence of serum, suggesting that the balance between cytokine- and serum-induced Bcl-2 expression and cytokine -induced Bax expression may determine whether a cell undergoes cytokine'-induced apoptosis.
Cell Death and DifferentiationBcr – Abl-mediated resistance to apoptosis is independent of PI 3-kinase activity
29 Citations1997Gustavo P. Amarante‐Mendes, Thomas Jascur +3 more
It is concluded that while PI3K participates in the anti-apoptotic response mediated by some growth factors and also seems to be important for the growth of Bcr-Abl-positive cells, it does not play any role in Bcr’s– A Bl-mediated resistance to apoptosis.
Cold Spring Harbor Symposia on Quantitative BiologyGenetic Analysis of Apoptotic and Survival Signals
8 Citations1999Tak W. Mak, Wen‐Chen Yeh
…