Display Settings:

Format

Send to:

Choose Destination
See comment in PubMed Commons below
Oncogene. 2000 Nov 23;19(50):5703-11.

Cyclin D1 suppresses retinoblastoma protein-mediated inhibition of TAFII250 kinase activity.

Author information

  • 1Department of Molecular Genetics and Biochemistry, University of Pittsburgh School of Medicine, Pennsylvania 15261, USA.

Abstract

The retinoblastoma tumor suppressor protein has been shown to bind directly and inhibit a transcriptionally-important amino-terminal kinase domain of TATA-binding protein-associated factor TAFII250. Cyclin D1 also is able to associate with the amino terminus of TAFII250 in a region very similar to or overlapping the Rb-binding site. In this study, we have examined whether cyclin D1 affects the functional interaction between Rb and TAFII250. We observed that when cyclin D1 is coincubated with Rb and TAFII250, the ability of Rb to inhibit TAFII250 kinase activity is effectively blocked. However, cyclin D1 by itself has no apparent effect on TAFII250 kinase activity. We further found that the Rb-related protein p107 can inhibit TAFII250 kinase activity, and this inhibition is likewise alleviated by cyclin D1. Cyclin D1 prevents the kinase-inhibitory effect of an Rb mutant unable to bind to D-type cyclins, indicating that it is acting through its association with TAFII250 and not with Rb. However, we found no evidence of TAFII250-binding competition between Rb and cyclin D1 in vitro. The adenovirus E1A protein, which also binds to both Rb and TAFII250, exhibited a suppressive effect on Rb-mediated kinase inhibition similar to that seen with cyclin D1. Our results suggest a novel means by which cyclin D1 may be able to independently regulate the activity of Rb.

PMID:
11126356
[PubMed - indexed for MEDLINE]
Free full text
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Nature Publishing Group
    Loading ...
    Write to the Help Desk