Abstract
| Originalsprog | Engelsk |
|---|---|
| Tidsskrift | Proceedings of the National Academy of Science of the United States of America |
| Vol/bind | 107 |
| Udgave nummer | 31 |
| Sider (fra-til) | 13854-9 |
| Antal sider | 5 |
| ISSN | 0027-8424 |
| DOI | |
| Status | Udgivet - 2010 |
Bibliografisk note
Keywords: Animals; Carboxypeptidases; Cell Adhesion Molecules; Cell Line; Down-Regulation; Humans; Membrane Glycoproteins; Mice; NF-kappa B; Nitric Oxide Synthase Type II; Protein Binding; RNA, Small InterferingAdgang til dokumentet
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I: Proceedings of the National Academy of Science of the United States of America, Bind 107, Nr. 31, 2010, s. 13854-9.
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review
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TY - JOUR
T1 - Regulation of NF-kappaB activity and inducible nitric oxide synthase by regulatory particle non-ATPase subunit 13 (Rpn13)
AU - Mazumdar, Tuhina
AU - Gorgun, F Murat
AU - Sha, Youbao
AU - Tyryshkin, Alexey
AU - Zeng, Shenyan
AU - Hartmann-Petersen, Rasmus
AU - Jørgensen, Jakob Ploug
AU - Hendil, Klavs B
AU - Eissa, N Tony
N1 - Keywords: Animals; Carboxypeptidases; Cell Adhesion Molecules; Cell Line; Down-Regulation; Humans; Membrane Glycoproteins; Mice; NF-kappa B; Nitric Oxide Synthase Type II; Protein Binding; RNA, Small Interfering
PY - 2010
Y1 - 2010
N2 - Human Rpn13, also known as adhesion regulating molecule 1 (ADRM1), was recently identified as a novel 19S proteasome cap-associated protein, which recruits the deubiquitinating enzyme UCH37 to the 26S proteasome. Knockdown of Rpn13 by siRNA does not lead to global accumulation of ubiquitinated cellular proteins or changes in proteasome expression, suggesting that Rpn13 must have a specialized role in proteasome function. Thus, Rpn13 participation in protein degradation, by recruiting UCH37, is rather selective to specific proteins whose degradation critically depends on UCH37 deubiquitination activity. The specific substrates for the Rpn13/UCH37 complex have not been determined. Because of a previous discovery of an interaction between Rpn13 and inducible nitric oxide synthase (iNOS), we hypothesized that iNOS is one of the substrates for the Rpn13/UCH37 complex. In this study, we show that Rpn13 is involved in iNOS degradation and is required for iNOS interaction with the deubiquitination protein UCH37. Furthermore, we discovered that IkappaB-alpha, a protein whose proteasomal degradation activates the transcription factor NF-kappaB, is also a substrate for the Rpn13/UCH37 complex. Thus, this study defines two substrates, with important roles in inflammation and host defense for the Rpn13/UCH37 pathway.
AB - Human Rpn13, also known as adhesion regulating molecule 1 (ADRM1), was recently identified as a novel 19S proteasome cap-associated protein, which recruits the deubiquitinating enzyme UCH37 to the 26S proteasome. Knockdown of Rpn13 by siRNA does not lead to global accumulation of ubiquitinated cellular proteins or changes in proteasome expression, suggesting that Rpn13 must have a specialized role in proteasome function. Thus, Rpn13 participation in protein degradation, by recruiting UCH37, is rather selective to specific proteins whose degradation critically depends on UCH37 deubiquitination activity. The specific substrates for the Rpn13/UCH37 complex have not been determined. Because of a previous discovery of an interaction between Rpn13 and inducible nitric oxide synthase (iNOS), we hypothesized that iNOS is one of the substrates for the Rpn13/UCH37 complex. In this study, we show that Rpn13 is involved in iNOS degradation and is required for iNOS interaction with the deubiquitination protein UCH37. Furthermore, we discovered that IkappaB-alpha, a protein whose proteasomal degradation activates the transcription factor NF-kappaB, is also a substrate for the Rpn13/UCH37 complex. Thus, this study defines two substrates, with important roles in inflammation and host defense for the Rpn13/UCH37 pathway.
U2 - 10.1073/pnas.0913495107
DO - 10.1073/pnas.0913495107
M3 - Journal article
C2 - 20634424
SN - 0027-8424
VL - 107
SP - 13854
EP - 13859
JO - Proceedings of the National Academy of Science of the United States of America
JF - Proceedings of the National Academy of Science of the United States of America
IS - 31
ER -