[Structures and functions of the 26S proteasome Rpn10 family].
The ubiquitin-dependent proteolytic pathway is thought to be one of the vital systems for cellular regulations, including control of the cell cycle, differentiation and apoptosis. In this pathway, poly-ubiquitinated proteins are selectively degraded by the 26S proteasome, a multisubunit proteolytic machinery. Recognition of the poly-ubiquitin chain by the 26S proteasome should be a key step leading to the selective degradation of target proteins, and the Rpn10 subunit of the 26S proteasome has been shown to preferentially bind the poly-ubiquitin chain in vitro. We previously reported that the mouse Rpn10 mRNA family is generated from a single gene by developmentally regulated, alternative splicing. To determine whether such alternative splicing mechanisms occur in organisms other than the mouse, we searched for Rpn10 isoforms in various species. Here we summarize the gene organization of the Rpn10 in lower species and provide evidence that the competence for generating all distinct forms of Rpn10 alternative splicing has expanded through evolution. Some of the Rpn10 family genes were found to be expressed in distinct developmental stages, suggesting that they have distinct functions during embryogenesis. For example, Rpn10c and Rpn10e were exclusively expressed at specific developmental stages and in specific tissues, while Rpn10a was expressed constitutively. Our experimental results indicate that the respective Rpn10 proteins possess distinct roles in the progression of development. Furthermore, some of the Rpn10 variants specifically interacted with important developmental regulators.
Kawahara
Hiroyuki
H
Department of Biochemistry, Graduate School of Pharmaceutical Sciences, Hokkaido University, Kita-12 Nishi-6, Kita-ku, Sapporo 060-0812, Japan. kawahara@pharm.hokudai.ac.jp
D017398:Alternative Splicing; D000818:Animals; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D005314:Embryonic and Fetal Development; D019143:Evolution, Molecular; D008025:Ligases / Q000502:physiology; D051379:Mice; D010447:Peptide Hydrolases / Q000737:chemistry / Q000502:physiology*; D046988:Proteasome Endopeptidase Complex; D020033:Protein Isoforms; D011506:Proteins / Q000378:metabolism*; D016601:RNA-Binding Proteins; D025801:Ubiquitin / Q000502:physiology*; D044767:Ubiquitin-Protein Ligases
D002352:Carrier Proteins; C498506:PSMD4 protein, human; D020033:Protein Isoforms; D011506:Proteins; D016601:RNA-Binding Proteins; D025801:Ubiquitin; D044767:Ubiquitin-Protein Ligases; D010447:Peptide Hydrolases; D046988:Proteasome Endopeptidase Complex; C061553:ATP dependent 26S protease; D008025:Ligases