C/EBPα arrests cell proliferation through direct inhibition of cdk2 and cdk4
C/EBPα arrests cell proliferation through direct inhibition of cdk2 and cdk4
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DOI：
10.1016/s1097-2765(01)00366-5
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发表时间：
2001-10-01
期刊：
影响因子：
16
通讯作者：
Timchenko, NA
中科院分区：
文献类型：
--
作者：
Wang, HM;Iakova, P;Timchenko, NA
转录因子CCAAT/增强子结合蛋白α（C/EBP α）是细胞增殖的强抑制剂。我们发现C/EBP α直接与cdk 2和cdk 4相互作用，并通过抑制这些激酶来抑制细胞增殖。我们在氨基酸175和187之间绘制了C/EBP α的短生长抑制区域。C/EBP α的这一部分负责直接抑制细胞周期蛋白依赖性激酶，并导致培养细胞的生长停滞。C/EBP α通过阻断cdk 2与细胞周期蛋白的结合来抑制cdk 2活性。重要的是，cdk 4和cdk 2的活性在C/EBP α敲除肝脏中增加，导致增殖增加。我们的数据表明，肝脏特异性转录因子C/EBP α通过直接抑制cdk 2和cdk 4来引起生长停滞。
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.