TNF 受体的激活可导致细胞死亡,细胞坏死的机制受遗传调节,不同于定义为坏死性凋亡的细胞凋亡。坏死性凋亡是近年来研究最多的新兴细胞死亡/信号通路之一,特别是考虑到这一过程在人类疾病中的作用。然而,并非所有与生理和病理条件相关的 TNF 信号转导的调节成分都已被确定。2008 年,Spata2(精子发生相关蛋白 2)被确定为调节细胞坏死和细胞凋亡的细胞信号网络的七个基本基因之一。该基因已被我们的小组克隆并命名为 Spata2,因为发现其表达在睾丸中与其他组织相比有所升高,定位于支持细胞水平并且依赖于 FSH。最近,已经证明 Spata2 基因的缺失会导致抑制素 α 表达增加和雄性小鼠的生育力减弱。然而,更重要的是,最近发表的五份报告强调了 SPATA2 对于将 CYLD 募集到 TNFR1 信号复合物从而促进其激活导致 TNF 诱导的细胞死亡至关重要。SPATA2 的缺失会增加 NF-kB 的转录激活并限制 TNF 诱导的坏死性凋亡。在这里,我们将讨论这些关于 SPATA2 的重要发现,特别是关注表明该蛋白质在 TNF 信号通路中发挥作用的证据。最近发表的五份报告强调了 SPATA2 对于将 CYLD 募集到 TNFR1 信号复合物从而促进其激活导致 TNF 诱导的细胞死亡至关重要。SPATA2 的缺失会增加 NF-kB 的转录激活并限制 TNF 诱导的坏死性凋亡。在这里,我们将讨论这些关于 SPATA2 的重要发现,特别是关注表明该蛋白质在 TNF 信号通路中发挥作用的证据。最近发表的五份报告强调了 SPATA2 对于将 CYLD 募集到 TNFR1 信号复合物从而促进其激活导致 TNF 诱导的细胞死亡至关重要。SPATA2 的缺失会增加 NF-kB 的转录激活并限制 TNF 诱导的坏死性凋亡。在这里,我们将讨论这些关于 SPATA2 的重要发现,特别是关注表明该蛋白质在 TNF 信号通路中发挥作用的证据。
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The role of SPATA2 in TNF signaling, cancer, and spermatogenesis
The activation of TNF receptors can lead to cell death with a mechanism of cell necrosis regulated genetically and distinct from apoptosis which is defined as necroptosis. Necroptosis has been one of the most studied emerging cell death/signaling pathways in recent years, especially in light of the role of this process in human disease. However, not all regulatory components of TNF signaling have been identified in relation to both physiological and pathological conditions. In 2008, Spata2 (Spermatogenesis-associated protein 2) was identified as one of the seven fundamental genes for the cellular signaling network that regulates necroptosis and apoptosis. This gene had been cloned by our group and named Spata2 as its expression was found to be elevated in the testis compared to other tissues, localized at the Sertoli cell level and FSH-dependent. More recently, it has been demonstrated that deletion of Spata2 gene causes increased inhibin α expression and attenuated fertility in male mice. However, more importantly, five recently published reports have highlighted that SPATA2 is crucial for recruiting CYLD to the TNFR1 signaling complex thus promoting its activation leading to TNF-induced cell death. Loss of SPATA2 increases transcriptional activation of NF-kB and limits TNF-induced necroptosis. Here we will discuss these important findings regarding SPATA2 and, in particular, focus attention on the evidence that suggests a role for this protein in the TNF signaling pathway.