Alternative exon usage and processing of the major histocompatibility complex-encoded proteasome subunits.
The finding that two subunits of the proteasome, LMP2 and LMP7, are encoded in the major histocompatibility complex (MHC) has linked the proteasome which represents a major extralysosomal proteolytic system to the processing of intracellular antigens. Here we describe a second form of the human LMP7 cDNA, LMP7-E2, which has been identified during the characterization of novel genes in the MHC. The analysis of the genome organization of LMP7 revealed that LMP7-E1 and LMP7-E2 arise by alternative exon usage. Using specific antibodies against LMP2 and LMP7, we show that they are co-expressed with class I MHC molecules as well as a putative peptide transporter. The polypeptides encoded by LMP7 and LMP2 undergo proteolytic processing when incorporated into proteasomes, and the LMP7 precursor is derived mainly from LMP7-E2. Furthermore, our data suggest that LMP7 and LMP2 are mutually dependent for their incorporation into the proteasomal complex.
Früh
K
K
Scripps Research Institute, La Jolla, California 92037.
Yang
Y
Y
Arnold
D
D
Chambers
J
J
Wu
L
L
Waters
J B
JB
Spies
T
T
Peterson
P A
PA
D000595:Amino Acid Sequence; D000956:Antigens, Viral / Q000235:genetics*; D001483:Base Sequence; D003546:Cysteine Endopeptidases / Q000235:genetics*; D005091:Exons; D015870:Gene Expression; D005796:Genes; D005802:Genes, MHC Class II; D008285:Major Histocompatibility Complex; D008565:Membrane Proteins / Q000235:genetics*; D008969:Molecular Sequence Data; D009097:Multienzyme Complexes / Q000235:genetics*; D009838:Oligodeoxyribonucleotides / Q000737:chemistry; D046988:Proteasome Endopeptidase Complex; D011498:Protein Precursors / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D011506:Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D014763:Viral Matrix Proteins
D000956:Antigens, Viral; C037662:EBV-associated membrane antigen, Epstein-Barr virus; D008565:Membrane Proteins; D009097:Multienzyme Complexes; D009838:Oligodeoxyribonucleotides; D011498:Protein Precursors; D011506:Proteins; D012333:RNA, Messenger; D014763:Viral Matrix Proteins; D003546:Cysteine Endopeptidases; C077436:LMP7 protein; D046988:Proteasome Endopeptidase Complex