Piscopo Denise M, Hinds Philip W
Molecular Oncology Research Institute, Tufts Medical Center, Boston, Massachusetts 02111, USA.
Cancer Res. 2008 Jul 15;68(14):5581-90. doi: 10.1158/0008-5472.CAN-07-6346.
Cyclin G1 was identified as a transcriptional target of p53 that encodes a protein with strong homology to the cyclin family of cell cycle regulators. We show that either ectopically expressed or endogenous cyclin G1 protein is very unstable, undergoes modification with ubiquitin, and is likely degraded by the proteasome. Ectopic cyclin G1 protein stability is increased by cyclin box mutation or by association with inactive cyclin-dependent kinase (CDK) subunits, suggesting that a function of cyclin G1 as a CDK regulator may be required for its rapid turnover. Furthermore, cyclin G1 and the cyclin box mutant interact with and are ubiquitinated by MDM2, another transcriptional target of p53 that acts as a negative regulator of p53 stability. These data suggest that the cyclin box has a role in the proteasome-mediated degradation of cyclin G1 and thus suggest a putative role for a CDK in cyclin G1 metabolism and function.
细胞周期蛋白G1被鉴定为p53的转录靶点，它编码一种与细胞周期调节因子的细胞周期蛋白家族具有高度同源性的蛋白质。我们发现，无论是异位表达还是内源性的细胞周期蛋白G1蛋白都非常不稳定，会被泛素修饰，并且可能被蛋白酶体降解。细胞周期蛋白盒突变或与无活性的细胞周期蛋白依赖性激酶（CDK）亚基结合可增加异位细胞周期蛋白G1蛋白的稳定性，这表明细胞周期蛋白G1作为CDK调节因子的功能可能是其快速周转所必需的。此外，细胞周期蛋白G1和细胞周期蛋白盒突变体与MDM2相互作用并被其泛素化，MDM2是p53的另一个转录靶点，作为p53稳定性的负调节因子。这些数据表明细胞周期蛋白盒在蛋白酶体介导的细胞周期蛋白G1降解中起作用，从而提示CDK在细胞周期蛋白G1代谢和功能中可能具有假定作用。
