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.
Department of Microbiology and Immunology, Pennsylvania State University College of Medicine, 500 University Drive, Hershey, PA 17033, USA.
Abraham
A
Fong
Minying
M
Zhang
John
J
Neely
Shao-Cong
SC
Sun
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