Department of Laboratory Medicine, Clinical Research Center, Lund University, SE-205 Malmö, Sweden.
Trends Biochem Sci. 2010 Jul;35(7):392-9. doi: 10.1016/j.tibs.2010.02.007. Epub 2010 Mar 26.
The tumor suppressor CYLD is a deubiquitylating enzyme that negatively regulates different signaling pathways by removing lysine 63-linked polyubiquitin chains from several specific substrates. In various tumor types, CYLD loss can lead to cell survival or cell proliferation. In addition to its loss due to mutations, CYLD expression can also be decreased through transcriptional and post-transcriptional regulatory mechanisms. Moreover, as epigenetic repression of CYLD can affect tumor progression in different cancer types, the activation of the CYLD promoter ensures the tight control of an inflammatory response. Recent work also shows that CYLD activity can be governed by different regulatory mechanisms including phosphorylation, thus providing another layer of control for diverse physiological processes.
抑癌基因 CYLD 是一种去泛素化酶，通过从几种特定底物上去除赖氨酸 63 连接的多泛素链，负调控不同的信号通路。在各种肿瘤类型中，CYLD 的缺失可导致细胞存活或增殖。除了因突变导致的缺失外，CYLD 的表达也可以通过转录和转录后调控机制来降低。此外，由于 CYLD 的表观遗传抑制作用会影响不同癌症类型的肿瘤进展，因此 CYLD 启动子的激活可确保对炎症反应的严格控制。最近的研究还表明，CYLD 的活性可以通过不同的调控机制来控制，包括磷酸化，从而为各种生理过程提供了另一层控制。
