S9, a 19 S proteasome subunit interacting with ubiquitinated NF-kappaB2/p100.
Proteasome-mediated processing of the nfkappab2 gene product p100 is a regulated event that generates the NF-kappaB subunit p52. This event can be induced through p100 phosphorylation by a signaling pathway involving the nuclear factor-kappaB-inducing kinase (NIK). The C-terminal region of p100, which contains its phosphorylation site and a death domain, plays a pivotal role in regulating the processing of p100. To understand the biochemical mechanism of p100 processing, we searched for cellular factors interacting with the C-terminal regulatory region of p100 using the yeast two-hybrid system. This led to the identification of S9, a non-ATPase subunit of the 19 S proteasome with no known functions. Interestingly, the S9/p100 interaction could be induced by NIK but not by a catalytically inactive NIK mutant. This inducible molecular interaction required p100 ubiquitination and was dependent on the intact death domain. We further demonstrated that the death domain is essential for NIK-induced post-translational processing of p100, thus providing a functional link between the S9 binding and the processing of p100. Finally, we provide genetic evidence for the essential role of S9 in the inducible processing of p100.
Fong
Abraham
A
Department of Microbiology and Immunology, Pennsylvania State University College of Medicine, 500 University Drive, Hershey, PA 17033, USA.
Zhang
Minying
M
Neely
John
J
Sun
Shao-Cong
SC
D001483:Base Sequence; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D006801:Humans; D009097:Multienzyme Complexes / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex; D011485:Protein Binding; D012313:RNA; D025801:Ubiquitin / Q000378:metabolism
D009097:Multienzyme Complexes; D016328:NF-kappa B; C034477:RNA primers; D025801:Ubiquitin; D012313:RNA; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex