Cyclin-dependent kinase inhibition by the KLF6 tumor suppressor protein through interaction with cyclin D1

Sharon Benzeno, Goutham Narla, Jorge Allina, George Z. Cheng, Helen L. Reeves, Michaela S. Banck, Joseph A. Odin, J. Alan Diehl, Doris Germain, Scott L. Friedman

Research output: Contribution to journalArticlepeer-review

122 Scopus citations

Abstract

Kruppel-like factor 6 (KLF6) is a tumor suppressor gene inactivated in prostate and colon cancers, as well as in astrocytic gliomas. Here, we establish that KLF6 mediates growth inhibition through an interaction with cyclin D1, leading to reduced phosphorylation of the retinoblastoma protein (Rb) at Ser795. Furthermore, introduction of KLF6 disrupts cyclin D1-cyclin-dependent kinase (cdk) 4 complexes and forces the redistribution of p21Cip/Kip onto cdk2, which promotes G1 cell cycle arrest. Our data suggest that KLF6 converges with the Rb pathway to inhibit cyclin D1/cdk4 activity, resulting in growth suppression.

Original languageEnglish (US)
Pages (from-to)3885-3891
Number of pages7
JournalCancer research
Volume64
Issue number11
DOIs
StatePublished - Jun 1 2004

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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