CREM, a master-switch of the transcriptional cascade in male germ cells
CREM, a master-switch of the transcriptional cascade in male germ cells
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DOI：
10.1007/bf03343781
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发表时间：
2000-10-01
影响因子：
5.4
通讯作者：
Sassone-Corsi, P
中科院分区：
文献类型：
--
作者：
De Cesare, D;Fimia, GM;Sassone-Corsi, P
在真核生物中，腺苷酸环化酶信号通路刺激后的转录调节由cAMP反应性核因子家族介导。CREB和CREM转录因子通过由环AMP、钙、生长因子和应激信号刺激的激酶对关键丝氨酸残基的磷酸化来激活。磷酸化允许CBP（CREB结合蛋白）的重新募集，CBP是一种与一般转录机制接触的大的共激活因子。CREM基因在下丘脑-垂体-性腺轴中起着关键的生理和发育作用。CREM在减数分裂后细胞中高度表达，这是由垂体激素FSH调节的显著发育开关。通过同源重组产生的CREM突变小鼠揭示精子发生在精子发生的第一步就停止了。晚期精子细胞完全缺失，而凋亡的生殖细胞显著增加。突变雄性小鼠完全缺乏精子，这一表型让人想起人类不育症的病例。有趣的是，在雄性生殖细胞中，CREM不是磷酸化的，而是与ACT相关联，ACT是具有内在转录活性的仅LIM类蛋白质的成员。因此，在某些情况下，CREM可以绕过磷酸化的经典要求并与CBP结合。(J.年. Invest. 23：592-596，2000）（C）2000，Editrice Kurtis.
In eukaryotes, transcriptional regulation upon stimulation of the adenylyl cyclase signalling pathway is mediated by a family of cAMP-responsive nuclear factors. The CREB and CREM transcription factors are activated by phosphorylation of a key serine residue by kinase stimulated by cyclic AMP, calcium, growth factors and stress signals. Phosphorylation allows recruiment of CBP (CREB Binding Protein), a large co-activator that contacts the general transcriptional machinery. The CREM gene plays a key physiological and developmental role within the hypothalamic-pituitary-gonadal axis. CREM is highly expressed in post-meiotric cells upon a striking developmental switch regulated by the pituitary hormone FSH. CREM-mutant mice generated by homologous recombination reveal that spermatogenesis stops at the first step of spermiogenesis. Late spermatids are completely absent while there is a significant increase in apoptotic germ cells. Mutant male mice completely lack spermatozoa, a phenotype reminescent of cases of human infertility. Interestingly, in male germ cells, CREM is not phosphorylated but associates with ACT, a member of the LIM-only class of proteins that has intrinsic transcriptional activity. Thus, in some circumstance, CREM can bypass the classical requirement for phosphorylation and association with CBP. (J. Endocrinol. Invest. 23: 592-596, 2000) (C) 2000, Editrice Kurtis.