Cytoplasmic domains of the transporter associated with antigen processing and P-glycoprotein interact with subunits of the proteasome.
The proteasome is a multi-protein complex that degrades cellular proteins as well as foreign proteins destined for antigen presentation. The latter function involves the immunoproteasome, in which several proteasome subunits are exchanged for gamma-interferon-induced subunits. The transporter associated with antigen processing (TAP) transports proteasome-generated peptides across the membrane of the endoplasmic reticulum (ER) prior to presentation on the plasma membrane. We demonstrate interactions between the cytoplasmic domains of TAP subunits and subunits of both the proteasome and the immunoproteasome, suggesting direct targeting of antigenic peptides to the ER via a TAP-proteasome association. We also show interaction between one of the cytoplasmic domains of P-glycoprotein and a proteasome subunit, but not the corresponding immunoproteasome subunit, suggesting a possible role for P-glycoprotein in the transport of proteasome-derived peptides.
Begley
Gail S
GS
Biology Department, Northeastern University, 330 Huntington Avenue, Boston, MA 02115, USA. g.begley@neu.edu
Horvath
Andrea R
AR
Taylor
Jenny C
JC
Higgins
Christopher F
CF
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism* / Q000502:physiology; D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D000071450:ATP Binding Cassette Transporter, Subfamily B, Member 3; D018528:ATP-Binding Cassette Transporters / Q000737:chemistry* / Q000276:immunology / Q000378:metabolism; D017951:Antigen Presentation; D000941:Antigens / Q000378:metabolism; D001692:Biological Transport; D003593:Cytoplasm; D004721:Endoplasmic Reticulum / Q000378:metabolism; D006801:Humans; D010446:Peptide Fragments / Q000276:immunology / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000276:immunology / Q000378:metabolism*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D021122:Protein Subunits
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D000071450:ATP Binding Cassette Transporter, Subfamily B, Member 3; D018528:ATP-Binding Cassette Transporters; D000941:Antigens; D010446:Peptide Fragments; D021122:Protein Subunits; C073119:TAP1 protein, human; C071692:TAP2 protein, human; D046988:Proteasome Endopeptidase Complex