Transcriptional repression of the D-type cyclin-dependent kinase inhibitor p16 by the retinoblastoma susceptibility gene product pRb.

Abstract:

:Progression of the eukaryotic cell division cycle is regulated by a series of structurally related serine/threonine protein kinases known as cyclin-dependent kinases (CDKs). The D-type cyclin-dependent kinases, CDK4 and CDK6, have been strongly implicated in the control of G1 progression and the phosphorylation of the retinoblastoma protein, pRb. The formation of complexes and enzymatic activity of cyclin D-CDK4 and cyclin D-CDK6 kinases is negatively regulated by p16INK4 (MTS1/CDK4I/CDKN2) via its specific interaction with CDK4 and CDK6 catalytic subunits. Here we report that the p16 mRNA accumulates to a high level in cells lacking pRb function and transcription of p16 is repressed by pRb. Our results provide evidence supporting a feedback regulatory loop involving pRb, p16, and cyclin-dependent kinases.

journal_name

Cancer Res

journal_title

Cancer research

authors

Li Y,Nichols MA,Shay JW,Xiong Y

subject

Has Abstract

pub_date

1994-12-01 00:00:00

pages

6078-82

issue

23

eissn

0008-5472

issn

1538-7445

journal_volume

54

pub_type

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