Letellier Elisabeth, Haan Serge
Molecular Disease Mechanisms Group, Life Sciences Research Unit, University of Luxembourg, 162A avenue de la Faïencerie, L-1511 Luxembourg, Luxembourg.
Molecular Disease Mechanisms Group, Life Sciences Research Unit, University of Luxembourg, 162A avenue de la Faïencerie, L-1511 Luxembourg, Luxembourg,
Front Biosci (Elite Ed). 2016 Jan 1;8(1):189-204. doi: 10.2741/E760.
Suppressors of cytokine signalling (SOCS) proteins are modulators of cytokine and growth factor signalling whose aberrant regulation has been linked to a variety of inflammatory and neoplastic diseases. SOCS proteins are able to act as substrate-recruiting component of E3-ubiquitin ligase complexes and target interacting proteins for degradation. At least some of the family members can also directly inhibit tyrosine kinases such as Janus Kinases (JAK). The most studied family members, CIS, SOCS1, SOCS2 and SOCS3 are important regulators of the JAK-STAT pathway. Here, we focus on SOCS2 and review its biological function as well as its implication in pathological processes. Furthermore, we take advantage of the known crystal structures of SOCS2 to discuss the potential effects of a selection of SOCS2 mutations that were identified in tumour tissues.
细胞因子信号转导抑制因子(SOCS)蛋白是细胞因子和生长因子信号转导的调节因子,其异常调节与多种炎症和肿瘤性疾病有关。SOCS蛋白能够作为E3泛素连接酶复合物的底物招募成分,并将相互作用的蛋白质靶向降解。至少一些家族成员还可以直接抑制酪氨酸激酶,如Janus激酶(JAK)。研究最多的家族成员CIS、SOCS1、SOCS2和SOCS3是JAK-STAT途径的重要调节因子。在这里,我们聚焦于SOCS2,并综述其生物学功能以及在病理过程中的意义。此外,我们利用已知的SOCS2晶体结构来讨论在肿瘤组织中鉴定出的一系列SOCS2突变的潜在影响。