An Atypical E3 Ligase Zinc Finger Protein 91 Stabilizes and Activates NF-κB-inducing Kinase via Lys63-linked Ubiquitination

• DOI: 10.1074/jbc.m110.129551
• Publication Date: 2010-08-04T02:31:48Z
• Authors: Xuejun Jin; Hong Ri Jin; Haeng Sun Jung; Se Jeong Lee; Jeong-Hyung Lee; Jung Joon Lee
• Keywords: IκB kinase; Deubiquitinating enzyme

The NF-κB transcription factors control many physiological processes, including inflammation, immunity, and apoptosis. Its activity contributes to the development of various cell malignancies. NF-κB-inducing kinase (NIK) plays a pivotal role in activation. However, molecular mechanism stabilize activate NIK remains elusive, although it is known that cIAP1/2 (cellular inhibitor apoptosis 1 2) ubiquitinate for degradation. Here, we report novel NF-κB-related zinc finger protein 91 (ZFP91) stabilizes activates ubiquitination-dependent manner. We show ZFP91 interacts with promotes Lys(63)-linked ubiquitination subsequent processing p100 p52. results vitro biochemical assays indicate functions as an E3 ligase directly NIK. Remarkably, coincides its Thr(559) phosphorylation. Furthermore, knockdown expression by RNA interference inhibits CD40 ligation-induced activation well noncanonical target genes. These data clearly important regulator pathway.