Cyclin-dependent kinase inhibition by the KLF6 tumor suppressor protein through interaction with cyclin D1
Cancer research, 2004•AACR
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 …
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 …
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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