PMID- 18380807
OWN - NLM
STAT- MEDLINE
DCOM- 20080911
LR  - 20181201
IS  - 0385-5600 (Print)
IS  - 0385-5600 (Linking)
VI  - 52
IP  - 2
DP  - 2008 Feb
TI  - Disruption of the association of 73 kDa heat shock cognate protein with 
      transporters associated with antigen processing (TAP) decreases TAP-dependent 
      translocation of antigenic peptides into the endoplasmic reticulum.
PG  - 94-106
LID - 10.1111/j.1348-0421.2008.00017.x [doi]
AB  - Major histocompatibility complex class I-bound antigenic peptides generated in 
      the cytosol are translocated into the ER by TAP. In the present study, the 
      physical association of HSC73 with TAP in human lymphoblastoid T1 cells was 
      demonstrated. The dissociation was induced in the presence of 10 mM ATP, 
      indicating that the ADP-binding form of HSC73 might be associated with TAP. We 
      found that HSC73-binding immunosuppressant, MeDSG disrupted the HSC73-TAP 
      association, whereas it did not affect the binding of HSC73 to a substrate 
      protein. MHC class I expression on the cell surface was also downregulated. Then, 
      the effect of MeDSG on the TAP-mediated ER translocation was examined using two 
      homologous model peptides, NGT-Bw4 and NGT-Bw6, which had distinct binding 
      affinity to HSC73. Although high-affinity peptide NGT-Bw4 was translocated by 
      TAP, low-affinity peptide NGT-Bw6 was not. The TAP-dependent translocation of 
      NGT-Bw4 was abolished in the presence of MeDSG. Decreased presentation on the 
      cell surface was shown for the human leukocyte antigen (HLA)-A31-restricted 
      natural antigenic peptide F4.2, which had high affinity to HSC73, in the presence 
      of MeDSG. It was indicated that disruption of the HSC73-TAP association resulted 
      in inhibition of TAP-dependent translocation of HSC73-bound peptides. Our 
      findings highlighted an important role of HSC73 for feeding antigenic peptides to 
      TAP, and suggested a possibility that a synthetic polyamine might inhibit the 
      function of HSC73, thereby suppressing MHC class I-restricted presentation of 
      HSC73-bound antigenic peptides.
FAU - Kamiguchi, Kenjiro
AU  - Kamiguchi K
AD  - Third Department of Internal Medicine, Asahikawa Medical College, Asahikawa, 
      Japan.
FAU - Torigoe, Toshihiko
AU  - Torigoe T
FAU - Fujiwara, Osamutaro
AU  - Fujiwara O
FAU - Ohshima, Shin
AU  - Ohshima S
FAU - Hirohashi, Yoshihiko
AU  - Hirohashi Y
FAU - Sahara, Hiroeki
AU  - Sahara H
FAU - Hirai, Itaru
AU  - Hirai I
FAU - Kohgo, Yutaka
AU  - Kohgo Y
FAU - Sato, Noriyuki
AU  - Sato N
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Australia
TA  - Microbiol Immunol
JT  - Microbiology and immunology
JID - 7703966
RN  - 0 (ATP Binding Cassette Transporter, Subfamily B, Member 2)
RN  - 0 (ATP-Binding Cassette Transporters)
RN  - 0 (Antigens)
RN  - 0 (Guanidines)
RN  - 0 (HSC70 Heat-Shock Proteins)
RN  - 0 (HSPA8 protein, human)
RN  - 0 (Histocompatibility Antigens Class I)
RN  - 0 (Immunosuppressive Agents)
RN  - 0 (Peptides)
RN  - 0 (TAP1 protein, human)
RN  - 114760-35-9 (methyldeoxyspergualin)
SB  - IM
MH  - ATP Binding Cassette Transporter, Subfamily B, Member 2
MH  - ATP-Binding Cassette Transporters/*metabolism
MH  - *Antigen Presentation
MH  - Antigens/*metabolism
MH  - Cell Line
MH  - Down-Regulation
MH  - Endoplasmic Reticulum/*metabolism
MH  - Guanidines/pharmacology
MH  - HSC70 Heat-Shock Proteins/genetics/*metabolism
MH  - Histocompatibility Antigens Class I/biosynthesis
MH  - Humans
MH  - Immunosuppressive Agents/pharmacology
MH  - Peptides/*metabolism
MH  - Protein Binding
EDAT- 2008/04/03 09:00
MHDA- 2008/09/13 09:00
CRDT- 2008/04/03 09:00
PHST- 2008/04/03 09:00 [pubmed]
PHST- 2008/09/13 09:00 [medline]
PHST- 2008/04/03 09:00 [entrez]
AID - MIM017 [pii]
AID - 10.1111/j.1348-0421.2008.00017.x [doi]
PST - ppublish
SO  - Microbiol Immunol. 2008 Feb;52(2):94-106. doi: 10.1111/j.1348-0421.2008.00017.x.