In:
Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 93, No. 23 ( 1996-11-12), p. 12861-12866
Abstract:
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 G 1 phase progression of the cell cycle.
Simian virus 40 (SV40) small tumor (t) antigen is capable of promoting G 1 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.
Type of Medium:
Online Resource
ISSN:
0027-8424
,
1091-6490
DOI:
10.1073/pnas.93.23.12861
Language:
English
Publisher:
Proceedings of the National Academy of Sciences
Publication Date:
1996
detail.hit.zdb_id:
209104-5
detail.hit.zdb_id:
1461794-8
SSG:
11
SSG:
12
