Skaug Brian, Jiang Xiaomo, Chen Zhijian J
Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390-9148, USA.
Annu Rev Biochem. 2009;78:769-96. doi: 10.1146/annurev.biochem.78.070907.102750.
Nuclear factor kappa enhancer binding protein (NF-kappaB) regulates diverse biological processes including immunity, inflammation, and apoptosis. A vast array of cellular stimuli converges on NF-kappaB, and ubiquitination plays an essential role in the coordination of these signals to regulate NF-kappaB activity. At least three steps in NF-kappaB activation directly involve ubiquitination: proteasomal degradation of inhibitor of NF-kappaB (IkappaB), processing of NF-kappaB precursors, and activation of the transforming growth factor (TGF)-beta-activated kinase (TAK1) and IkappaB kinase (IKK) complexes. In this review, we discuss recent advances in the identification and characterization of ubiquitination and deubiquitination machinery that regulate NF-kappaB. Particular emphasis is given to proteasome-independent functions of ubiquitin, specifically its role in the activation of protein kinase complexes and in coordination of cell survival and apoptosis signals downstream of tumor necrosis factor alpha (TNFalpha).
核因子κB增强子结合蛋白（NF-κB）调节多种生物学过程，包括免疫、炎症和细胞凋亡。大量细胞刺激信号汇聚于NF-κB，泛素化在协调这些信号以调节NF-κB活性方面发挥着至关重要的作用。NF-κB激活过程中至少有三个步骤直接涉及泛素化：NF-κB抑制蛋白（IκB）的蛋白酶体降解、NF-κB前体的加工处理，以及转化生长因子（TGF）-β激活激酶（TAK1）和IκB激酶（IKK）复合物的激活。在本综述中，我们讨论了调节NF-κB的泛素化和去泛素化机制的鉴定与表征方面的最新进展。特别强调了泛素不依赖蛋白酶体的功能，尤其是其在蛋白激酶复合物激活以及肿瘤坏死因子α（TNFα）下游细胞存活和凋亡信号协调中的作用。
