Induction of cyclin D1 by simian virus 40 small tumor antigen

Genichi Watanabe, Alan Howe, Richard J. Lee, Chris Albanese, I. Wei Shu, Anthony Karnezis, Leonard Zon, John Kyriakis, Kathleen Rundell, Richard G. Pestell

Research output: Contribution to journalArticlepeer-review

195 Scopus citations


Cell-cycle progression is mediated by a coordinated interaction between cyclin-dependent kinases and their target proteins including the pRB and E2F/DP-1 complexes. Immunoneutralization and antisense experiments have established that the abundance of cyclin D1, a regulatory subunit of the cyclin-dependent kinases, may be rate-limiting for G1 phase progression of the cell cycle. Simian virus 40 (SV40) small tumor (t) antigen is capable of promoting G1 phase progression and augments substantially the efficiency of SV40 transformation through several distinct domains. In these studies, small t antigen stimulated cyclin D1 promoter activity 7-fold, primarily through an AP-1 binding site at -954 with additional contributions from a CRE site at - 57. The cyclin D1 AP-1 and CRE sites were sufficient for activation by small t antigen when linked to an heterologous promoter. Point mutations of small t antigen between residues 97-103 that reduced PP2A binding were partially defective in the induction of the cyclin D1 promoter. These mutations also reduced activation of MEK1 and two distinct members of the mitogen-activated protein kinase family, the ERKs (extracellular signal regulated kinases) and the SAPKs (stress-activated protein kinases), in transfected cells. Dominant negative mutants of either MEK1, ERK or SEK1, reduced small t-dependent induction of the cyclin D1 promoter. SV40 small t induction of the cyclin D1 promoter involves both the ERK and SAPK pathways that together may contribute to the proliferative and transformation enhancing activity of small t antigen.

Original languageEnglish (US)
Pages (from-to)12861-12866
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number23
StatePublished - Nov 12 1996
Externally publishedYes

ASJC Scopus subject areas

  • General


Dive into the research topics of 'Induction of cyclin D1 by simian virus 40 small tumor antigen'. Together they form a unique fingerprint.

Cite this