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SUMO1 modification of NF‐κB2/p100 is essential for stimuli‐induced p100 phosphorylation and processing
Author(s) -
Vatsyayan Jaya,
Qing Guoliang,
Xiao Gutian,
Hu Jing
Publication year - 2008
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.1038/embor.2008.122
Subject(s) - sumo protein , phosphorylation , signal transduction , microbiology and biotechnology , ubiquitin , biology , kinase , sumo enzymes , biochemistry , gene
A primary step in activating the alternative nuclear factor‐κB (NF‐κB) pathway requires NF‐κB2/p100 processing to generate p52. In most cases, stimuli‐induced p100 processing is dependent on NF‐κB‐inducing kinase/IκB kinase α‐mediated phosphorylation and ubiquitination. Here, we report that post‐translational modification of p100 at specific sites by the small ubiquitin‐like modifier (SUMO) is another determining factor for stimuli‐induced p100 processing. The results show that basal SUMO modification is required for stimuli‐induced p100 phosphorylation and that blocking SUMOylation of p100, either by site‐directed mutation or by short interfering RNA‐targeted diminution of E2 SUMO‐conjugating enzyme Ubc9, inhibits various physiological stimuli‐induced p100 processing and ultimate activation of the alternative NF‐κB pathway. Together, these findings show the crucial role of SUMO1 modification in p100 processing and provide mechanistic insights into the participation of SUMO1 modification in the regulation of signal transduction.