Mysterious liaisons: the relationship between c-Myc and the cell cycle
OncogenePublished 13 May 1999Open access
Álvaro J. Obaya, Maria K. Mateyak, John M. Sedivy
Citations257
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TL;DR
The mechanisms by which c-Myc interacts with the intrinsic cyclin/Cdk cell cycle machinery remain undefined.
Abstract
A large body of physiological evidence shows that either upregulation or downregulation of intracellular c-Myc activity has profound consequences on cell cycle progression. Recent work suggests that c-Myc may stimulate the activity of cyclin E/cyclin-dependent kinase 2 (Cdk2) complexes and antagonize the action of the Cdk inhibitor p27KIP1. Cyclin D/Cdk4/6 complexes have also been implicated as targets of c-Myc activity. However, in spite of considerable effort, the mechanisms by which c-Myc interacts with the intrinsic cyclin/Cdk cell cycle machinery remain undefined.
Keywords
MedicineBiochemistry, Genetics and Molecular Biology
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224 Citations1994Matthew Meyerson, Ed Harlow
The activation ofcdk6 kinase occurs during mid-G1 in phytohemagglutinin-stimulated T cells, well prior to the activation of cdk2 kinase, which suggests that cdk6, and by analogy its homolog cdk4, links growth factor stimulation with the onset of cell cycle progression.
Molecular EndocrinologyIdentification of residues in the estrogen receptor that confer differential sensitivity to estrogen and hydroxytamoxifen.
215 Citations1993Paul S. Danielian, R White +3 more
Mutation of the glycine at position 525 and the methionine and/or serine at positions 521/522 virtually abolishes the ability of the receptor to bind estradiol and stimulate transcription, and the mutant receptors retain the partial agonist activity exhibited by the wild-type receptor in the presence of 4-hydroxytamoxifen.
The EMBO JournalCyclin E and c‐Myc promote cell proliferation in the presence of p16INK4a and of hypophosphorylated retinoblastoma family proteins
207 Citations1997Konstantinos Alevizopoulos, Jaromir Vlach +2 more
The data imply that oncogenic activation of c‐Myc, and possibly also of cyclin E, mimics loss of the p16/pRb pathway during oncogenesis and possesses an E2F‐independent function required to enter S‐phase.
NatureRequirement for tyrosine phosphorylation of Cdk4 in Gl arrest induced by ultraviolet irradiation
186 Citations1995Yasuhiko Terada, Masaaki Tatsuka +2 more
It is shown that tyrosine phosphorylation of Cdk4 is required for this arrest of mammalian fibroblasts in the Gl phase of the cell cycle, as well as the S and G2 phases.
Genes & Developmentc-<i>myc</i> null cells misregulate <i>cad</i> and <i>gadd45</i> but not other proposed c-Myc targets
175 Citations1998Andrew B. G. Bush, Maria K. Mateyak +5 more
It is reported here that the expression of virtually all proposed c-Myc target genes is unchanged in cells containing a homozygous null deletion of c-myc, and it is demonstrated that a loss-of-function approach is critical for the evaluation of potential c- MYC target genes.
Biochimica et Biophysica Acta (BBA) - Reviews on CancerCell cycle regulation by the retinoblastoma family of growth inhibitory proteins
175 Citations1996Roderick L. Beijersbergen, René Bernards
The retinoblastoma family of growth-inhibitory proteins act by binding and inhibiting several proteins with growth-stimulatory activity, the most prominent of which is the cellular transcription factor E2F.
OncogeneCdk2-dependent phosphorylation of p27 facilitates its Myc-induced release from cyclin E/cdk2 complexes
168 Citations1997Daniel A. Müller, Caroline Bouchard +7 more
It is shown that cyclin E/cdk2 phosphorylates p27 at a carboxy-terminal threonine residue (T187) in vitro; mutation of this residue to valine stabilises cyclin W/w/w complexes and suggests that cdk2 bound to p27 is catalytically active.
OncogeneMyc represses the growth arrest gene gadd45
152 Citations1997Wilson W. Marhin, Shaojun Chen +3 more
Myc suppression of gadd45 defines a novel pathway through which Myc promotes cell cycle entry and prevents growth arrest of transformed cells and is mediated by a p53-independent pathway.
ScienceDown-regulation of LFA-1 Adhesion Receptors by C- <i>myc</i> Oncogene in Human B Lymphoblastoid Cells
135 Citations1990Giorgio Inghirami, F Grignani +4 more
Since LFA-1 is involved in B cell adhesion to cytotoxic T cells, natural killer cells, and vascular endothelium, these results imply functions for c-myc in normal B cell development and lymphomagenesis.
The EMBO JournalActivation of cyclin‐dependent kinases by Myc mediates induction of cyclin A, but not apoptosis.
128 Citations1996Bettina Rudolph, Rainer Saffrich +5 more
The data show that active G1 cyclin/cdk complexes are both necessary and sufficient for induction of cyclin A by Myc, and that activation of cdks and induction of apoptosis are largely independent events that occur in response to induction of Myc.
OncogeneRepression of c-Myc responsive genes in cycling cells causes G1 arrest through reduction of cyclin E/CDK2 kinase activity
116 Citations1997Katrien Berns, E. Marielle Hijmans +1 more
It is shown that inhibition of c-Myc activity in exponentially growing cells leads to G1 arrest through loss of cyclin E-associated kinase activity, and that MadMyc does not cause alterations in the expression levels of Cyclin E, CDK2, p27kip1, cyclin D1 or CDK4 in G1-arrested cells.
Proceedings of the National Academy of SciencesRescue of defective mitogenic signaling by D-type cyclins.
113 Citations1995Martine F. Roussel, A M Theodoras +2 more
Myc and D-type cyclins collaborate during the mitogenic response to CSF-1, whereas cyclin E functions in a separate pathway, suggesting that expression of the two genes is interdependent.
Molecular and Cellular BiologyRequirement of Cyclin E-Cdk2 Inhibition in p16 <sup> <i>INK4a</i> </sup> -Mediated Growth Suppression
112 Citations1998Hong Jiang, Hubert S. Chou +1 more
Functional differences between p16 and Cdk4N158 are determined and it is demonstrated that inhibition of cyclin D-dependent kinase activity may not be sufficient to cause G1 arrest in actively proliferating tumor cells.
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