title: Characterization of the testis-specific proteasome subunit α4s in mammals.
abstract: The 26 S proteasome is responsible for regulated proteolysis in eukaryotic cells. It is composed of one 20 S core particle (CP) flanked by one or two 19 S regulatory particles. The CP is composed of seven different α-type subunits (α1-α7) and seven different β-type subunits, three of which are catalytic. Vertebrates encode four additional catalytic β subunits that are expressed predominantly in immune tissues and produce distinct subtypes of CPs particularly well suited for the acquired immune system. In contrast, the diversity of α subunits remains poorly understood. Recently, another α subunit, referred to as α4s, was reported. However, little is known about α4s. Here we provide a detailed characterization of α4s and the α4s-containing CP. α4s is exclusively expressed in germ cells that enter the meiotic prophase and is incorporated into the CP in place of α4. A comparison of structural models revealed that the differences in the primary sequences between α4 and α4s are located on the outer surface of the CP, suggesting that α4s interacts with specific molecules via these unique regions. α4s-containing CPs account for the majority of the CPs in mouse sperm. The catalytic β subunits in the α4s-containing CP are β1, β2, and β5, and immunosubunits are not included in the α4s-containing CP. α4s-containing CPs have a set of peptidase activities almost identical to those of α4-containing CPs. Our results provide a basis for understanding the role of α4s and male germ cell-specific proteasomes in mammals.
authors.affiliation: From the Laboratory of Protein Metabolism, Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Uechi
authors.forename: Jun
authors.initials: J
authors.lastname: Hamazaki
authors.forename: Shigeo
authors.initials: S
authors.lastname: Murata
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D003546:Cysteine Endopeptidases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D057809:HEK293 Cells; D006801:Humans; D008297:Male; D008540:Meiosis; D051379:Mice; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000494:pharmacology; D061988:Proteasome Inhibitors / Q000494:pharmacology; D011487:Protein Conformation; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid; D013094:Spermatozoa / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D013737:Testis / Q000166:cytology / Q000201:enzymology*
chemical_list: D009842:Oligopeptides; D061988:Proteasome Inhibitors; D021122:Protein Subunits; D003546:Cysteine Endopeptidases; C488661:alpha4 subunit, proteasome 20S, human; C078846:epoxomicin
keywords: Proteasome; Sperm; Spermatogenesis; Testis; Ubiquitin