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A Systematic Substrate Screen Links Cyclin D-Dependent Kinases to Senescence Suppression in Cancer Cells through FOXM1

ABSTRACT: Gene expression (mRNA profiling) of U2OS osteosarcoma cells treated with 1 mM of the CDK4/6-specific inhibitor, PD0332991, versus vehicle (DMSO) for 4 hours Here, we monitored the early transcriptional response to acute inhibition of CDK4/6 catalytic activity. As PD0332991 substantially induced senescence in U2OS cells, we performed gene expression arrays from U2OS cells treated with or without PD0332991 for 4 hours. Although this did not result in significant changes in the cell cycle profile, it led to significant changes in global gene expression. 10 total samples were analyzed, i.e. we compared five PD0332991-treated versus five vehicle-treated U2OS cell samples (gene level).

ORGANISM(S): Homo sapiens

SUBMITTER: Lars Anders

PROVIDER: E-GEOD-32182 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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A systematic screen for CDK4/6 substrates links FOXM1 phosphorylation to senescence suppression in cancer cells.

Anders Lars L Ke Nan N Hydbring Per P Choi Yoon J YJ Widlund Hans R HR Chick Joel M JM Zhai Huili H Vidal Marc M Gygi Stephen P SP Braun Pascal P Sicinski Piotr P

Cancer cell 20111101 5

Cyclin D-dependent kinases (CDK4 and CDK6) are positive regulators of cell cycle entry and they are overactive in the majority of human cancers. However, it is currently not completely understood by which cellular mechanisms CDK4/6 promote tumorigenesis, largely due to the limited number of identified substrates. Here we performed a systematic screen for substrates of cyclin D1-CDK4 and cyclin D3-CDK6. We identified the Forkhead Box M1 (FOXM1) transcription factor as a common critical phosphoryl ...[more]

PMID: 22094256

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