SUMO1 modification of NF-kappaB2/p100 is essential for stimuli-induced p100 phosphorylation and processing.
A primary step in activating the alternative nuclear factor-kappaB (NF-kappaB) pathway requires NF-kappaB2/p100 processing to generate p52. In most cases, stimuli-induced p100 processing is dependent on NF-kappaB-inducing kinase/IkappaB kinase alpha-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-kappaB 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.
Vatsyayan
Jaya
J
Department of Pharmacology, University of Pittsburgh Cancer Institute, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 19014, USA.
Qing
Guoliang
G
Xiao
Gutian
G
Hu
Jing
J
D000818:Animals; D002460:Cell Line; D006801:Humans; D015151:Immunoblotting; D047468:Immunoprecipitation; D051379:Mice; D016297:Mutagenesis, Site-Directed; D052003:NF-kappa B p52 Subunit / Q000378:metabolism*; D041681:NIH 3T3 Cells; D010766:Phosphorylation; D011485:Protein Binding; D011499:Protein Processing, Post-Translational; D034741:RNA, Small Interfering / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D025842:SUMO-1 Protein / Q000235:genetics / Q000378:metabolism*; D044763:Ubiquitin-Conjugating Enzymes / Q000235:genetics / Q000378:metabolism*; D000098843:Ubiquitin-Conjugating Enzyme UBC9
D052003:NF-kappa B p52 Subunit; D034741:RNA, Small Interfering; D025842:SUMO-1 Protein; D044763:Ubiquitin-Conjugating Enzymes; D000098843:Ubiquitin-Conjugating Enzyme UBC9