title: Alternative exon usage and processing of the major histocompatibility complex-encoded proteasome subunits.
abstract: 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.
authors.affiliation: Scripps Research Institute, La Jolla, California 92037.
authors.forename: K
authors.initials: K
authors.lastname: Früh
authors.forename: Y
authors.initials: Y
authors.lastname: Yang
authors.forename: D
authors.initials: D
authors.lastname: Arnold
authors.forename: J
authors.initials: J
authors.lastname: Chambers
authors.forename: L
authors.initials: L
authors.lastname: Wu
authors.forename: J B
authors.initials: JB
authors.lastname: Waters
authors.forename: T
authors.initials: T
authors.lastname: Spies
authors.forename: P A
authors.initials: PA
authors.lastname: Peterson
mesh_terms: 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
chemical_list: 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