Cumulative effect of phosphorylation of pRB on regulation of E2F activity.

Abstract:

:The product of the retinoblastoma susceptibility gene, pRB, is a nuclear phosphoprotein that controls cell growth by binding to and suppressing the activities of transcription factors such as the E2F family. Transactivation activity is inhibited when E2F is bound to hypophosphorylated pRB and released when pRB is phosphorylated by cyclin-dependent kinases (CDKs). To determine which of 16 potential CDK phosphorylation sites regulated the pRB-E2F interaction, mutant pRB proteins produced by site-directed mutagenesis were tested for the ability to suppress E2F-mediated transcription in a reporter chloramphenicol acetyltransferase assay. Surprisingly, no one CDK site regulated the interaction of pRB with E2F when E2F was bound to DNA. Instead, disruption of transcriptional repression resulted from accumulation of phosphate groups on the RB molecule.

journal_name

Mol Cell Biol

authors

Brown VD,Phillips RA,Gallie BL

doi

10.1128/mcb.19.5.3246

subject

Has Abstract

pub_date

1999-05-01 00:00:00

pages

3246-56

issue

5

eissn

0270-7306

issn

1098-5549

journal_volume

19

pub_type

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