Herzinger T, Funk J O, Hillmer K, Eick D, Wolf D A, Kind P
Institut für Klinische Molekularbiologie und Tumorgenetik, GSF-Forschungszentrum für Umwelt und Gesundheit, München, Germany.
Oncogene. 1995 Nov 16;11(10):2151-6.
In response to genotoxic stress, cell cycle progression can be arrested at certain checkpoints which serve to maintain genomic integrity. We have investigated the mechanism of ultraviolet B (UVB) irradiation-induced cell cycle arrest in normal human keratinocytes and in the HaCaT keratinocyte cell line which carries mutant p53 tumour suppressor protein. While only normal keratinocytes showed a delay in G1 following sublethal UVB irradiation both cell types exhibited prolonged G2 arrest attributable to rapid inhibition of cyclin B-associated cdc2 kinase activity. This inhibition coincided with increased tyrosine phosphorylation of cdc2 and was reversed by the cdc25C phosphatase in vitro. The data indicate that UVB-induced G2 arrest in mammalian cells is mediated by inhibitory tyrosine phosphorylation of cdc2 and acts as a defense mechanism against DNA damage irrespective of the cells' p53 status.
作为对基因毒性应激的反应，细胞周期进程可在某些检查点停滞，这些检查点有助于维持基因组完整性。我们研究了紫外线B（UVB）照射诱导正常人角质形成细胞和携带突变型p53肿瘤抑制蛋白的HaCaT角质形成细胞系细胞周期停滞的机制。虽然亚致死剂量UVB照射后只有正常角质形成细胞在G1期出现延迟，但两种细胞类型均表现出G2期延长停滞，这归因于细胞周期蛋白B相关的cdc2激酶活性的快速抑制。这种抑制与cdc2酪氨酸磷酸化增加同时发生，并且在体外被cdc25C磷酸酶逆转。数据表明，UVB诱导的哺乳动物细胞G2期停滞是由cdc2的抑制性酪氨酸磷酸化介导的，并且无论细胞的p53状态如何，都作为针对DNA损伤的防御机制。
