摘要
DNA依赖性蛋白激酶(DNA-dependent protein kinase,DNA-PK)是由3个亚基组成的丝/苏氨酸蛋白激酶,属于磷脂酰肌醇-3激酶相关激酶家族(phosphatidylinositol 3-kinase-related kinases,PIKK),是基因组DNA损伤修复过程中的关键蛋白激酶,参与并决定着非同源末端连接DNA损伤修复通路的整个进程.此外DNA-PK还参与了电离辐射诱导的凋亡信号转导通路,免疫细胞V(D)J重组、免疫细胞分化、胰岛素刺激下的细胞应答等过程,具有维持端粒稳定性的功能.DNA-PK活性的升高会降低肿瘤对放射的敏感性,其活性主要受自身磷酸化调控,此外活性氧、EGFR、MG132抑制剂、PP1γ1和PP5等蛋白磷酸酶也有调控DNA-PK活性的作用.
DNA-dependent protein kinase ( DNA-PK), a serine/threonine kinase consisting of three subunits, is a member of the PIKKs (phosphoinositide 3-kinase-like family of protein kinases) . DNA-PK is the key protein kinase in the genomic DNA damage repair, participating in and determining the whole process of non-homologous end-joining. Furthermore, DNA-PK is involved in ionizing radiation stimulated apoptotie signal transduction, V (D) J recombination, immune cell differentiation, insulin-stimulated cellular responses, and maintenance of telomere stabili- ty. Increase of DNA-PK activity reduces the sensitivity of tumors to radiation. The activity of DNA-PK is mainly regulated by its autophosphorylation. Reactive oxygen species, EGFR, MG132 inhibitor, and protein phosphatase such as PP1 T1 PP5 also play a role in control of DNA-PK activity.
出处
《医学分子生物学杂志》
CAS
CSCD
2011年第3期278-282,共5页
Journal of Medical Molecular Biology