An atypical E3 ligase zinc finger protein 91 stabilizes and activates NF-κB-inducing kinase via Lys63-linked ubiquitination

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Title
An atypical E3 ligase zinc finger protein 91 stabilizes and activates NF-κB-inducing kinase via Lys63-linked ubiquitination
Author(s)
X Jin; H R Jin; H S Jung; S J Lee; J H Lee; Jung Joon Lee
Bibliographic Citation
Journal of Biological Chemistry, vol. 285, no. 40, pp. 30539-30547
Publication Year
2010
Abstract
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 NF-κB activation. However, the molecular mechanism to stabilize and activate NIK remains elusive, although it is known that cIAP1/2 (cellular inhibitor of apoptosis 1 and 2) ubiquitinate NIK for degradation. Here, we report a novel NF-κB-related zinc finger protein 91 (ZFP91) that stabilizes and activates NIK in a ubiquitination-dependent manner. We show that ZFP91 interacts with and promotes the Lys63-linked ubiquitination of NIK and subsequent processing of p100 to p52. The results of in vitro biochemical assays indicate that ZFP91 functions as an E3 ligase directly to NIK. Remarkably, the ubiquitination of NIK coincides with its Thr559 phosphorylation. Furthermore, knockdown of ZFP91 expression by RNA interference inhibits the CD40 ligation-induced activation of NIK and p100 processing as well as the expression of noncanonical NF-κB target genes. These data clearly indicate that ZFP91 is an important regulator of the noncanonical NF-κB pathway
ISSN
0021-9258
Publisher
Amer Soc Biochemistry Molecular Biology Inc
DOI
http://dx.doi.org/10.1074/jbc.M110.129551
Type
Article
Appears in Collections:
1. Journal Articles > Journal Articles
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