Developmentally regulated, alternative splicing of the Rpn10 gene generates multiple forms of 26S proteasomes.
The 26S proteasome is a multisubunit protein- destroying machinery that degrades ubiquitin-tagged proteins. To date only a single species of Rpn10, which possibly functions as a multiubiquitin chain-binding subunit, has been identified in various organisms. Here we report that mouse Rpn10 mRNAs occur in at least five distinct forms, named Rpn10a to Rpn10e, and that they are generated from a single gene by developmentally regulated, alternative splicing. Rpn10a is ubiquitously expressed, whereas Rpn10e is expressed only in embryos, with the highest levels of expression in the brain. Both forms of Rpn10 are components of the 26S proteasome, with an apparently similar affinity for multiubiquitylated [(125)I]lysozyme in vitro. However, they exert markedly divergent effects on the destruction of B-type cyclin in Xenopus egg extracts. Thus, the 26S proteasome occurs in at least two functionally distinct forms: one containing a ubiquitously expressed Rpn10a and the other a newly identified, embryo-specific Rpn10e. While the former is thought to perform proteolysis constitutively in a wide variety of cells, the latter may play a specialized role in early embryonic development.
Institute of Molecular and Cellular Biosciences, The University of Tokyo, Tokyo 113-0032, Japan.
H
H
Kawahara
M
M
Kasahara
A
A
Nishiyama
K
K
Ohsumi
T
T
Goto
T
T
Kishimoto
Y
Y
Saeki
H
H
Yokosawa
N
N
Shimbara
S
S
Murata
T
T
Chiba
K
K
Suzuki
K
K
Tanaka
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics*; D017124:Conserved Sequence; D019926:Cyclin B / Q000378:metabolism; D019143:Evolution, Molecular; D018507:Gene Expression Regulation, Developmental; D051379:Mice; D008969:Molecular Sequence Data; D010447:Peptide Hydrolases / Q000235:genetics*; D046988:Proteasome Endopeptidase Complex; D016601:RNA-Binding Proteins; D017386:Sequence Homology, Amino Acid; D014452:Ubiquitins / Q000378:metabolism
D002352:Carrier Proteins; D019926:Cyclin B; C498506:PSMD4 protein, human; D016601:RNA-Binding Proteins; D014452:Ubiquitins; D010447:Peptide Hydrolases; D046988:Proteasome Endopeptidase Complex; C061553:ATP dependent 26S protease