Fautsch M P, Eblen S T, Anders R A, Burnette R J, Leof E B
Thoracic Diseases Research Unit, Mayo Clinic, Rochester, Minnesota 55905, USA.
J Cell Biochem. 1995 Aug;58(4):517-26. doi: 10.1002/jcb.240580415.
Cyclin-dependent kinases (cdks) are a family of proteins whose function plays a critical role in cell cycle traverse. Transforming growth factor-beta 1 (TGF-beta 1) is a potent growth inhibitor of epithelial cells. Since cdks have been suggested as possible biochemical markers for TGF-beta growth inhibition, we investigated the effect of TGF-beta 1 on cdc2 and cdk2 in a normal mouse mammary epithelial cell line (MME) and a TGF-beta-resistant MME cell line (BG18.2). TGF-beta 1 decreases newly synthesized cdc2 protein levels within 6 h after addition. Coincident with this decrease in newly synthesized cdc2 protein was a marked reduction in its ability to phosphorylate histone H1. This decrease in kinase activity is not due to a change in steady-state levels of cdc2 protein, since mRNA and total protein levels of cdc2 are not reduced until 12 h after TGF-beta 1 addition. This suggests that the kinase activity of cdc2 is dependent on newly synthesized cdc2 protein. Moreover, the protein synthesis of another cyclin-dependent kinase, cdk2, is not effected by TGF-beta 1 addition, but its kinase activity is substantially reduced. Thus, it appears that TGF-beta decreases the kinase activity of both cdc2 and cdk2 by distinct mechanisms.
细胞周期蛋白依赖性激酶（cdks）是一类蛋白质，其功能在细胞周期进程中起着关键作用。转化生长因子-β1（TGF-β1）是上皮细胞的一种强效生长抑制剂。由于cdks被认为可能是TGF-β生长抑制的生化标志物，我们研究了TGF-β1对正常小鼠乳腺上皮细胞系（MME）和TGF-β抗性MME细胞系（BG18.2）中cdc2和cdk2的影响。添加TGF-β1后6小时内，新合成的cdc2蛋白水平降低。与新合成的cdc2蛋白水平降低同时出现的是，其磷酸化组蛋白H1的能力显著下降。激酶活性的这种降低并非由于cdc2蛋白稳态水平的变化，因为直到添加TGF-β1后12小时，cdc2的mRNA和总蛋白水平才降低。这表明cdc2的激酶活性依赖于新合成的cdc2蛋白。此外，另一种细胞周期蛋白依赖性激酶cdk2的蛋白质合成不受添加TGF-β1的影响，但其激酶活性大幅降低。因此，似乎TGF-β通过不同机制降低了cdc2和cdk2的激酶活性。
