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Finding NEMO by K63-linked polyubiquitin chain.

Authors
Chen-F; Bhatia-D; Chang-Q; Castranova-V
Source
Cell Death Differ 2006 Nov; 13(11):1835-1838
NIOSHTIC No.
20031102
Abstract
Few would argue that protein ubiquitination is the most important process in the signaling pathway to activate nuclear factor-B (NF-B), a critical transcription factor governing the expression of genes involved in inflammation, carcinogenesis and cell apoptosis. Ubiquitination of IB, an intrinsic inhibitor of NF-B, was found more than one decade ago.1 In response to extracellular inducers, IB is first phosphorylated on the N-terminal two serine (S) residues, S32 and S36, by IKK kinase complex composed of two catalytic subunits, IKK and IKK, and one regulatory subunit, NEMO (IKK). This phosphorylation leads to the conjugation of lysine (K)48-linked polyubiquitin chains on two lysine (K) residues, K21 and K22, of IB protein. The conjugated polyubiquitin chains will ferry IB to the protein disposal machinery, proteasome, for degradation, leading to the activation and nuclear translocation of NF-B. The most abundant form of NF-B is the p50/p65(RelA) heterodimer, although other forms of NF-B dimers, such as p50/p50, p52/p52, p52/p65, p50/c-Rel, c-Rel/c-Rel and p50/RelB, have also been found. Later studies suggested that SCF-TrCP, a F-box ubiquitin ligase complex that uses phosphorylated S32 and S36 as a docking site, is responsible for the ubiquitination of IB protein.2
Keywords
Cell-differentiation; Cell-damage; Genes; Carcinogens; Carcinogenicity; Carcinogenesis; Proteins
Contact
F Chen, The Health Effect Laboratory Division, National Institute for Occupational Safety and Health, 1095 Willowdale Road, Morgantown, WV 26505
CODEN
CDDIEK
Publication Date
20061101
Document Type
Journal Article
Email Address
lfd3@cdc.gov
Fiscal Year
2007
NTIS Accession No.
NTIS Price
Issue of Publication
11
ISSN
1350-9047
NIOSH Division
HELD
Source Name
Cell Death and Differentiation
State
WV
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