Finding NEMO by K63-Linked Polyubiquitin Chain

Details

• Personal Author:
  Bhatia D ; Castranova, Vincent ; Chang Q ; Chen F
• Description:
  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 [Description provided by NIOSH]
• Subjects:
  Carcinogens Genetics Occupational Health Safety
• Keywords:
  Carcinogenesis Carcinogenicity Cell-damage Cell-differentiation Genes Proteins
• ISSN:
  1350-9047
• Document Type:
  Text
• Genre:
  Journal Article
• Place as Subject:
  OSHA Region 3 ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  13
• Issue:
  11
• NIOSHTIC Number:
  nn:20031102
• Citation:
  Cell Death Differ 2006 Nov; 13(11):1835-1838
• Contact Point Address:
  F Chen, The Health Effect Laboratory Division, National Institute for Occupational Safety and Health, 1095 Willowdale Road, Morgantown, WV 26505
• Email:
  lfd3@cdc.gov
• Federal Fiscal Year:
  2007
• Peer Reviewed:
  True
• Source Full Name:
  Cell Death and Differentiation
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:5d1c974d4445d7731039bfb6055ed0c5c3cd8bfdc46532fb82a4fcd3ca74316a4693b0bb99454c5d4b2ce12cbdf71d1d89871a27b7ab076d4801b8f002bd221b
• Download URL:
  https://stacks.cdc.gov/view/cdc/191457/cdc_191457_DS1.pdf
• File Type:
  [PDF - 85.58 KB ]