SET蛋白及其对雄激素合成的调节作用

Regulation of SET Protein on Androgen Production

SET蛋白在多种组织细胞中表达,包括中枢神经系统、肾上腺以及性腺的类固醇合成细胞。SET蛋白是细胞内多任务因子,参与多种生物过程,包括细胞周期、细胞凋亡、核DNA复制、基因转录以及表观遗传调节、肿瘤生成和转移等,在睾丸和卵巢中参与调节雄激素合成。SET蛋白负性调节PP2A的活性,但并不改变PP2A的表达量;通过增强CYP17A1和3β-HSD的转录促进雄激素的合成。CKⅡ和SET相互结合,使SET磷酸化,增强了SET对PP2A的抑制作用;hn RNPA2通过RNP1序列与SET结合,增强SET对PP2A的抑制作用,调节雄激素合成。

SET protein is expressed in many tissues and cells, including central nervous system,steroidogenesis cells of adrenal gland and gonads（testis and ovary）. SET protein is an intracellular factor with multiple functions, involved in those biological processes such as cell cycle, apoptosis, DNA replication,transcription, epigenetic regulation, oncogenesis and metastasis by many signal pathways. It was newly found that SET protein played a role in regulating androgen production in testis and ovary. SET protein down-regulated the activity of PP2A（did not affect the expression of PP2A）, and up-regulated the expressions of CYP17A1 and HSD3β2, which promoted steroidogenesis in gonads. Many regulators of SET protein, such as CK Ⅱ and hn RNPA2, participated in the pathways of SET protein. CK Ⅱ enhances the inhibition of SET protein to PP2 A activity by inducing phosphorylation of SET protein, while hn RNPA2 plays same role by the combination between its RNP1 sequence and SET protein.