Abstract:
:The anaphase-promoting complex or cyclosome (APC/C) initiates mitotic exit by ubiquitylating cell-cycle regulators such as cyclin B1 and securin. Lys 48-linked ubiquitin chains represent the canonical signal targeting proteins for degradation by the proteasome, but they are not required for the degradation of cyclin B1. Lys 11-linked ubiquitin chains have been implicated in degradation of APC/C substrates, but the Lys 11-chain-forming E2 UBE2S is not essential for mitotic exit, raising questions about the nature of the ubiquitin signal that targets APC/C substrates for degradation. Here we demonstrate that multiple monoubiquitylation of cyclin B1, catalysed by UBCH10 or UBC4/5, is sufficient to target cyclin B1 for destruction by the proteasome. When the number of ubiquitylatable lysines in cyclin B1 is restricted, Lys 11-linked ubiquitin polymers elaborated by UBE2S become increasingly important. We therefore explain how a substrate that contains multiple ubiquitin acceptor sites confers flexibility in the requirement for particular E2 enzymes in modulating the rate of ubiquitin-dependent proteolysis.
journal_name
Nat Cell Bioljournal_title
Nature cell biologyauthors
Dimova NV,Hathaway NA,Lee BH,Kirkpatrick DS,Berkowitz ML,Gygi SP,Finley D,King RWdoi
10.1038/ncb2425subject
Has Abstractpub_date
2012-01-29 00:00:00pages
168-76issue
2eissn
1465-7392issn
1476-4679pii
ncb2425journal_volume
14pub_type
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