The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Cell Cycle. 2011 Sep 15;10(18):3057-66. doi: 10.4161/cc.10.18.17320.
The constitutive photomorphogenesis 9 signalosome (COP9 or CSN) is an evolutionarily conserved multiprotein complex found in plants and animals. Because of the homology between the COP9 signalosome and the 19S lid complex of the proteosome, COP9 has been postulated to play a role in regulating the degradation of polyubiquitinated proteins. Many tumor suppressor and oncogene products are regulated by ubiquitination- and proteosome-mediated protein degradation. Therefore, it is conceivable that COP9 plays a significant role in cancer, regulating processes relevant to carcinogenesis and cancer progression (e.g., cell cycle control, signal transduction and apoptosis). In mammalian cells, it consists of eight subunits (CSN1 to CSN8). The relevance and importance of some subunits of COP9 to cancer are emerging. However, the mechanistic regulation of each subunit in cancer remains unclear. Among the CSN subunits, CSN5 and CSN6 are the only two that each contain an MPN (Mpr1p and Pad1p N-terminal) domain. The deneddylation activity of an MPN domain toward cullin-RING ubiquitin ligases (CRL) may coordinate CRL-mediated ubiquitination activity. More recent evidence shows that CSN5 and CSN6 are implicated in ubiquitin-mediated proteolysis of important mediators in carcinogenesis and cancer progression. Here, we discuss the mechanisms by which some CSN subunits are involved in cancer to provide a much needed perspective regarding COP9 in cancer research, hoping that these insights will lay the groundwork for cancer intervention.
组成型光形态发生 9 信号体（COP9 或 CSN）是一种在植物和动物中发现的进化上保守的多蛋白复合物。由于 COP9 信号体与蛋白酶体的 19S 盖子复合物之间的同源性，COP9 被推测在调节多泛素化蛋白的降解中发挥作用。许多肿瘤抑制因子和癌基因产物受泛素化和蛋白酶体介导的蛋白降解调节。因此，可以想象 COP9 在癌症中发挥重要作用，调节与致癌和癌症进展相关的过程（例如细胞周期控制、信号转导和细胞凋亡）。在哺乳动物细胞中，它由八个亚基（CSN1 到 CSN8）组成。COP9 的一些亚基与癌症的相关性和重要性正在显现。然而，每个亚基在癌症中的机制调节仍不清楚。在 CSN 亚基中，CSN5 和 CSN6 是仅包含一个 MPN（Mpr1p 和 Pad1p N 端）结构域的两个亚基。MPN 结构域对 cullin-RING 泛素连接酶（CRL）的去泛素化活性可能协调 CRL 介导的泛素化活性。最近的证据表明，CSN5 和 CSN6 参与了致癌和癌症进展中重要介质的泛素介导的蛋白水解。在这里，我们讨论了一些 CSN 亚基参与癌症的机制，为 COP9 在癌症研究中提供了急需的视角，希望这些见解为癌症干预奠定基础。
