Repression of c-myc responsive genes in cycling cells causes g1 arrest through reduction of cyclin e/cdk2 kinase activity

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. Access through your institution Buy or subscribe This is a preview of subscription content, access via your

institution ACCESS OPTIONS Access through your institution Subscribe to this journal Receive 50 print issues and online access $259.00 per year only $5.18 per issue Learn more Buy this

article * Purchase on SpringerLink * Instant access to full article PDF Buy now Prices may be subject to local taxes which are calculated during checkout ADDITIONAL ACCESS OPTIONS: * Log in

* Learn about institutional subscriptions * Read our FAQs * Contact customer support SIMILAR CONTENT BEING VIEWED BY OTHERS NON-CANONICAL PATHWAY FOR RB INACTIVATION AND EXTERNAL SIGNALING

COORDINATE CELL-CYCLE ENTRY WITHOUT CDK4/6 ACTIVITY Article Open access 29 November 2023 GFI1 UPREGULATES C-MYC EXPRESSION AND PROMOTES C-MYC-DRIVEN CELL PROLIFERATION Article Open access 13

October 2020 LOSS OF CDK4/6 ACTIVITY IN S/G2 PHASE LEADS TO CELL CYCLE REVERSAL Article Open access 05 July 2023 AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Division of Molecular

Carcinogenesis, The Netherlands Cancer Institute, Plesmanlaan 121, Amsterdam, 1066 CX, The Netherlands Katrien Berns, E Marielle Hijmans & René Bernards Authors * Katrien Berns View

author publications You can also search for this author inPubMed Google Scholar * E Marielle Hijmans View author publications You can also search for this author inPubMed Google Scholar *

René Bernards View author publications You can also search for this author inPubMed Google Scholar RIGHTS AND PERMISSIONS Reprints 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 Download citation * Received: 13 February 1997 * Revised: 14 May 1997 * Accepted: 14 May 1997 * Issue Date: 11 September 1997 * DOI:

https://doi.org/10.1038/sj.onc.1201280 SHARE THIS ARTICLE Anyone you share the following link with will be able to read this content: Get shareable link Sorry, a shareable link is not

currently available for this article. Copy to clipboard Provided by the Springer Nature SharedIt content-sharing initiative KEYWORDS * c-Myc * cell cycle * cyclin * CDK