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

doi:10.1158/0008-5472.CAN-03-2818

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

Medical Oncology

Research output: Contribution to journal › Article › peer-review

124 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 p21^Cip/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 language	English (US)
Pages (from-to)	3885-3891
Number of pages	7
Journal	Cancer research
Volume	64
Issue number	11
DOIs	https://doi.org/10.1158/0008-5472.CAN-03-2818
State	Published - Jun 1 2004

ASJC Scopus subject areas

Oncology
Cancer Research

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10.1158/0008-5472.CAN-03-2818

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

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.",

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T1 - Cyclin-dependent kinase inhibition by the KLF6 tumor suppressor protein through interaction with cyclin D1

AU - Benzeno, Sharon

AU - Narla, Goutham

AU - Allina, Jorge

AU - Cheng, George Z.

AU - Reeves, Helen L.

AU - Banck, Michaela S.

AU - Odin, Joseph A.

AU - Diehl, J. Alan

AU - Germain, Doris

AU - Friedman, Scott L.

PY - 2004/6/1

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AB - 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.

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

Abstract

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