PMID- 10671572
OWN - NLM
STAT- MEDLINE
DCOM- 20000321
LR  - 20210209
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 275
IP  - 7
DP  - 2000 Feb 18
TI  - Essential role of human leukocyte antigen-encoded proteasome subunits in 
      NF-kappaB activation and prevention of tumor necrosis factor-alpha-induced 
      apoptosis.
PG  - 5238-47
AB  - The multisubunit proteasome complex is the principal mediator of nonlysosomal 
      protein degradation. The proteasome subunit varies minimally between cells with 
      the exception of LMP2, LMP7, and LMP10 subunits in rodent and human cells. LMP2 
      and LMP7 subunits are encoded by the human lymphocyte antigen region, and they 
      optimize proteolytic mediated antigen presentation. The proteasome is also 
      important for the function of transcription factor nuclear factor-kappaB 
      (NF-kappaB). It is required for NF-kappaB subunits p50 and p52 generation and 
      catalyzes degradation of phosphorylated IkappaBalpha. These proteasome-mediated 
      reactions have now been shown to be defective in T2 cells, a human lymphocyte 
      cell line that lacks both LMP2 and LMP7. Although T2 cells contain normal 
      expression of p100 and p105, the abundance of p50 and p52 was greatly reduced. 
      Tumor necrosis factor-alpha (TNF-alpha) induced normal phosphorylation of 
      IkappaBalpha but failed to induce degradation of phosphorylated IkappaBalpha. 
      Both DNA binding assays and luciferase assays revealed that TNF-alpha-induced 
      NF-kappaB activation is defective in T2 cells. Unlike parental cells, T2 cells 
      were susceptible to TNF-alpha-induced apoptosis. These data indicate human 
      leukocyte antigen-linked proteasome subunits are essential for NF-kappaB 
      activation and protection of cells from TNF-alpha-induced apoptosis.
FAU - Hayashi, T
AU  - Hayashi T
AD  - Immunobiology Laboratory, Massachusetts General Hospital and Harvard Medical 
      School, Charlestown, Massachusetts 02129, USA.
FAU - Faustman, D
AU  - Faustman D
LA  - eng
GR  - R01 DE11151/DE/NIDCR NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Antigens)
RN  - 0 (DNA Primers)
RN  - 0 (Multienzyme Complexes)
RN  - 0 (NF-kappa B)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - EC 3.4.22.- (Cysteine Endopeptidases)
RN  - EC 3.4.25.1 (Proteasome Endopeptidase Complex)
SB  - IM
MH  - Animals
MH  - Antigens/*immunology
MH  - Apoptosis/*physiology
MH  - Base Sequence
MH  - Cell Line
MH  - Cysteine Endopeptidases/*physiology
MH  - DNA Primers
MH  - Humans
MH  - Leukocytes/*immunology
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Multienzyme Complexes/*physiology
MH  - NF-kappa B/*metabolism
MH  - Proteasome Endopeptidase Complex
MH  - Protein Processing, Post-Translational
MH  - Transcriptional Activation
MH  - Tumor Necrosis Factor-alpha/*physiology
EDAT- 2000/02/15 09:00
MHDA- 2000/03/25 09:00
CRDT- 2000/02/15 09:00
PHST- 2000/02/15 09:00 [pubmed]
PHST- 2000/03/25 09:00 [medline]
PHST- 2000/02/15 09:00 [entrez]
AID - S0021-9258(18)30749-X [pii]
AID - 10.1074/jbc.275.7.5238 [doi]
PST - ppublish
SO  - J Biol Chem. 2000 Feb 18;275(7):5238-47. doi: 10.1074/jbc.275.7.5238.