Regulation of early wave of germ cell apoptosis and spermatogenesis by deubiquitinating enzyme CYLD
Regulation of early wave of germ cell apoptosis and spermatogenesis by deubiquitinating enzyme CYLD
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DOI：
10.1016/j.devcel.2007.09.007
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发表时间：
2007-11-01
影响因子：
11.8
通讯作者：
Sun, Shao-Cong
中科院分区：
文献类型：
--
作者：
Wright, Ato;Reiley, William W.;Sun, Shao-Cong
精子发生涉及生殖细胞凋亡的早期波，这是维持生殖细胞和支持性支持细胞之间平衡所必需的。然而，调控这一凋亡事件的信号机制尚不明确。在这里，我们发现Cyld（一种最近发现的去泛素化酶）的遗传缺陷会减弱小鼠生殖细胞凋亡的早期浪潮，并导致精子发生受损。有趣的是，睾丸细胞中CYLD的缺失导致转录因子nf - κ B的激活和抗凋亡基因的异常表达。我们进一步发现CYLD负调控泛素依赖性nf - κ B激活因子RIP1。CYLD与RIP1结合，抑制RIP1的泛素化和信号功能。这些发现表明CYLD是一种关键的去泛素化酶（DUB），可调节生殖细胞凋亡和精子发生，并提示CYLD在控制睾丸RIP1/ nf - κ B信号轴中发挥重要作用。
Spermatogenesis involves an early wave of germ cell apoptosis, which is required for maintaining the balance between germ cells and supporting Sertoli cells. However, the signaling mechanism regulating this apoptotic event is poorly defined. Here we show that genetic deficiency of Cyld, a recently identified deubiquitinating enzyme, attenuates the early wave of germ cell apoptosis and causes impaired spermatogenesis in mice. Interestingly, the loss of CYLD in testicular cells leads to activation of the transcription factor NF-kappa B and aberrant expression of antiapoptotic genes. We further show that CYLD negatively regulates a ubiquitin-dependent NF-kappa B activator, RIP1. CYLD binds to RIP1 and inhibits its ubiquitination and signaling function. These findings establish CYLD as a pivotal deubiquitinating enzyme (DUB) that regulates germ cell apoptosis and spermatogenesis and suggest an essential role for CYLD in controlling the RIP1/NF-kappa B signaling axis in testis.