PMID- 8706130
OWN - NLM
STAT- MEDLINE
DCOM- 19960906
LR  - 20190705
IS  - 0092-8674 (Print)
IS  - 0092-8674 (Linking)
VI  - 86
IP  - 2
DP  - 1996 Jul 26
TI  - Coordinated dual cleavages induced by the proteasome regulator PA28 lead to 
      dominant MHC ligands.
PG  - 253-62
AB  - The eukaryotic 20S proteasome is known to associate with the IFN gamma-inducible 
      regulator PA28. We analyzed the kinetics of product generation by 20S proteasomes 
      with and without PA28. In the absence of PA28, the 20S proteasome rapidly 
      generates peptides that have been cleaved only once, while internal fragments 
      accumulate only slowly. In the presence of PA28, products generated by two 
      flanking cleavages appear immediately as main products while the generation of 
      single-cleavage products is strongly reduced. Kinetic data support a 
      PA28-induced, coordinated double-cleavage mechanism. In particular, degradation 
      of peptides derived from mouse cytomegalovirus pp89 and JAK1 kinase in the 
      presence of PA28 leads to strongly enhanced production of the respective major 
      histocompatibility complex ligands and potential precursors. These results show 
      that PA28 profoundly alters the cleavage mechanism of the proteasome and appears 
      to optimize the generation of dominant T-cell epitopes.
FAU - Dick, T P
AU  - Dick TP
AD  - Department of Tumorvirus-Immunology, German Cancer Research Center, Heidelberg, 
      Federal Republic of Germany.
FAU - Ruppert, T
AU  - Ruppert T
FAU - Groettrup, M
AU  - Groettrup M
FAU - Kloetzel, P M
AU  - Kloetzel PM
FAU - Kuehn, L
AU  - Kuehn L
FAU - Koszinowski, U H
AU  - Koszinowski UH
FAU - Stevanovic, S
AU  - Stevanovic S
FAU - Schild, H
AU  - Schild H
FAU - Rammensee, H G
AU  - Rammensee HG
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Cell
JT  - Cell
JID - 0413066
RN  - 0 (Autoantigens)
RN  - 0 (Epitopes)
RN  - 0 (Histocompatibility Antigens)
RN  - 0 (Ki antigen)
RN  - 0 (Ligands)
RN  - 0 (Muscle Proteins)
RN  - 0 (PSME1 protein, human)
RN  - 0 (Peptides)
RN  - 0 (Proteins)
RN  - EC 3.4.25.1 (Proteasome Endopeptidase Complex)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Autoantigens
MH  - Chromatography, High Pressure Liquid
MH  - Epitopes/metabolism
MH  - Female
MH  - Fibroblasts/chemistry/enzymology
MH  - Histocompatibility Antigens/*metabolism
MH  - Humans
MH  - Kinetics
MH  - Ligands
MH  - Mass Spectrometry
MH  - Mice
MH  - Molecular Sequence Data
MH  - *Muscle Proteins
MH  - Peptides/metabolism
MH  - Placenta/chemistry
MH  - Pregnancy
MH  - Proteasome Endopeptidase Complex
MH  - Proteins/*physiology
MH  - Substrate Specificity
MH  - T-Lymphocytes/enzymology/immunology
EDAT- 1996/07/26 00:00
MHDA- 1996/07/26 00:01
CRDT- 1996/07/26 00:00
PHST- 1996/07/26 00:00 [pubmed]
PHST- 1996/07/26 00:01 [medline]
PHST- 1996/07/26 00:00 [entrez]
AID - S0092-8674(00)80097-5 [pii]
AID - 10.1016/s0092-8674(00)80097-5 [doi]
PST - ppublish
SO  - Cell. 1996 Jul 26;86(2):253-62. doi: 10.1016/s0092-8674(00)80097-5.