Tomar Dhanendra, Singh Rajesh
Department of Cell Biology, School of Biological Sciences and Biotechnology, Indian Institute of Advanced Research, Gandhinagar, India.
Biol Cell. 2015 Jan;107(1):22-40. doi: 10.1111/boc.201400046. Epub 2014 Nov 14.
The nuclear factor κB (NF-κB) transcription factor family plays a key role in regulation of the inflammatory pathway in response to different physiological stimuli starting from development to ageing. The dysregulation of NF-κB has been associated with many pathological conditions like inflammatory diseases, neurodegeneration, metabolic diseases and various kinds of malignancies. The NF-κB pathway is regulated by number of post-translational modifications, including phosphorylation and ubiquitination. Ubiquitin (Ub) E3 ligases are key regulators of the process of ubiquitination and provide specificity to the pathway as they recognise the substrate and determine the topology of ubiquitination. TRIMs, members of RING family of Ub E3 ligases, are characterised by the presence of three conserved domains, RING, B-Box and coiled-coil (RBCC). Emerging evidence suggests that TRIMs regulate innate immune signalling during infection and different pathological conditions. The studies have demonstrated the role of TRIMs in regulation of inflammatory pathways including NF-κB. Recent reports suggest that TRIMs play a critical role in regulation of the NF-κB pathway by ubiquitinating proteins at different steps. In the current review, we discuss the role of TRIMs as novel NF-κB regulators and their role in different pathophysiological conditions.
核因子κB（NF-κB）转录因子家族在响应从发育到衰老的不同生理刺激时对炎症通路的调节中起关键作用。NF-κB的失调与许多病理状况相关，如炎症性疾病、神经退行性变、代谢性疾病和各类恶性肿瘤。NF-κB通路受多种翻译后修饰的调控，包括磷酸化和泛素化。泛素（Ub）E3连接酶是泛素化过程的关键调节因子，由于它们识别底物并决定泛素化的拓扑结构，因而为该通路提供了特异性。TRIMs是Ub E3连接酶RING家族的成员，其特征是存在三个保守结构域，即RING、B-Box和卷曲螺旋（RBCC）。新出现的证据表明，TRIMs在感染和不同病理状况下调节先天性免疫信号传导。这些研究已经证明了TRIMs在包括NF-κB在内的炎症通路调节中的作用。最近的报道表明，TRIMs在不同步骤通过对蛋白质进行泛素化在NF-κB通路的调节中起关键作用。在本综述中，我们讨论了TRIMs作为新型NF-κB调节因子的作用及其在不同病理生理状况中的作用。
