Journal
MOLECULAR CELL
Volume 8, Issue 4, Pages 817-828Publisher
CELL PRESS
DOI: 10.1016/S1097-2765(01)00366-5
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Funding
- NIA NIH HHS [AG 00756] Funding Source: Medline
- NIGMS NIH HHS [GM 55188] Funding Source: Medline
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The transcription factor CCAAT/enhancer binding protein alpha (C/EBP alpha) is a strong inhibitor of cell proliferation. We found that C/EBP alpha directly interacts with cdk2 and cdk4 and arrests cell proliferation by inhibiting these kinases. We mapped a short growth inhibitory region of C/EBP alpha between amino acids 175 and 187. This portion of C/EBP alpha is responsible for direct inhibition of cyclin-dependent kinases and causes growth arrest in cultured cells. C/EBP alpha inhibits cdk2 activity by blocking the association of cdk2 with cyclins. Importantly, the activities of cdk4 and cdk2 are increased in C/EBP alpha knockout livers, leading to increased proliferation. Our data demonstrate that the liver-specific transcription factor C/EBP alpha brings about growth arrest through direct inhibition of cdk2 and cdk4.
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