Rpn10-mediated degradation of ubiquitinated proteins is essential for mouse development.

摘要: Rpn10 is a subunit of the 26S proteasome that recognizes polyubiquitinated proteins. The importance in ubiquitin-mediated proteolysis debatable, since deficiency causes different phenotypes organisms. To date, role mammalian has not been examined genetically. Moreover, vertebrates have five splice variants whose expressions are developmentally regulated, but their biological significance understood. address these issues, we generated three kinds mutant mice. knockout resulted early-embryonic lethality, demonstrating essential mouse development. Rpn10a knock-in mice, which exclusively expressed constitutive type and did express vertebrate-specific variants, grew normally, indicating diversity for conventional Mice expressing N-terminal portion Rpn10, contained von Willebrand factor A (VWA) domain lacked ubiquitin-interacting motifs (Rpn10DeltaUIM), also exhibited embryonic suggesting important contribution UIM domains to viability, survived longer than Rpn10-null consistent with "facilitator" function VWA domain. Biochemical analysis Rpn10DeltaUIM liver showed specific impairment degradation ubiquitinated Our results demonstrate Rpn10-mediated proteins, catalyzed by UIMs, indispensable life.