Abstract
The c-myc gene encodes a sequence-specific DNA binding protein involved in proliferation and oncogenesis. Activation of c-myc expression in quiescent cells is sufficient to mediate cell cycle entry, whereas inhibition of c-myc expression causes cycling cells to withdraw from the cell cycle. To search for components of the cell cycle machinery that are targets of c-Myc, we have made a mutant c-Myc protein, named MadMyc, that actively represses c-myc target genes. Expression of MadMyc in cycling NIH3T3 cells causes a significant accumulation of cells in G1. The MadMyc-induced G1 arrest is rescued by ectopic expression of cyclin E/CDK2 and cyclin D1/CDK4, but not by Cdc25A, a known cell cycle target of c-Myc. The MadMyc G1 arrest does not require the presence of a functional retinoblastoma protein and is associated with a strong reduction in cyclin E/CDK2 kinase activity in arrested cells. MadMyc does not cause alterations in the expression levels of cyclin E, CDK2, p27kip1, cyclin D1 or CDK4 in G1-arrested cells. These data indicate that inhibition of c-Myc activity in exponentially growing cells leads to G1 arrest through loss of cyclin E-associated kinase activity.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 50 print issues and online access
$259.00 per year
only $5.18 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Berns, K., Hijmans, E. & Bernards, R. Repression of c-Myc responsive genes in cycling cells causes G1 arrest through reduction of cyclin E/CDK2 kinase activity. Oncogene 15, 1347–1356 (1997). https://doi.org/10.1038/sj.onc.1201280
Received:
Revised:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/sj.onc.1201280
Keywords
This article is cited by
-
siRNA against TSG101 reduces proliferation and induces G0/G1 arrest in renal cell carcinoma – involvement of c-myc, cyclin E1, and CDK2
Cellular & Molecular Biology Letters (2019)
-
MASTL induces Colon Cancer progression and Chemoresistance by promoting Wnt/β-catenin signaling
Molecular Cancer (2018)
-
Critical role of Myc activation in mouse hepatocarcinogenesis induced by the activation of AKT and RAS pathways
Oncogene (2017)
-
A proteomic study of cMyc improvement of CHO culture
BMC Biotechnology (2010)
-
Functional and molecular interactions between the HGF/c-Met pathway and c-Myc in large-cell medulloblastoma
Laboratory Investigation (2008)