biostudies-literatureUnknown25(21)Hara TKPC2 (Kip1 ubiquitylation-promoting complex 2) together with KPC1 forms the ubiquitin ligase KPC, which regulates degradation of the cyclin-dependent kinase inhibitor p27 at the G(1) phase of the cell cycle. KPC2 contains a ubiquitin-like (UBL) domain, two ubiquitin-associated (UBA) domains, and a heat shock chaperonin-binding (STI1) domain. We now show that KPC2 interacts with KPC1 through its UBL domain, with the 26S proteasome through its UBL and NH(2)-terminal UBA domains, and with polyubiquitylated proteins through its UBA domains. The association of KPC2 with KPC1 was found to stabilize KPC1 in a manner dependent on the STI1 domain of KPC2. KPC2 mutants that lacked either the NH(2)-terminal or the COOH-terminal UBA domain supported the polyubiquitylation of p27 in vitro, whereas a KPMolecular and cellular biology9292-303https://www.ebi.ac.uk/biostudies/studies/S-EPMC1265808biostudies-literatureRole of the UBL-UBA protein KPC2 in degradation of p27 at G1 phase of the cell cycle.PMC1265808Kotoshiba SFujiwara KMizushima NOnoyama IShirakawa MHara TNakayama KIKamura TTakahashi HfalseRole of the UBL-UBA protein KPC2 in degradation of p27 at G1 phase of the cell cycle.KPC2 (Kip1 ubiquitylation-promoting complex 2) together with KPC1 forms the ubiquitin ligase KPC, which regulates degradation of the cyclin-dependent kinase inhibitor p27 at the G(1) phase of the cell cycle. KPC2 contains a ubiquitin-like (UBL) domain, two ubiquitin-associated (UBA) domains, and a heat shock chaperonin-binding (STI1) domain. We now show that KPC2 interacts with KPC1 through its UBL domain, with the 26S proteasome through its UBL and NH(2)-terminal UBA domains, and with polyubiquitylated proteins through its UBA domains. The association of KPC2 with KPC1 was found to stabilize KPC1 in a manner dependent on the STI1 domain of KPC2. KPC2 mutants that lacked either the NH(2)-terminal or the COOH-terminal UBA domain supported the polyubiquitylation of p27 in vitro, whereas a KP2005-01-01T00:00:00Z2005 Nov2025-04-25T21:21:16.964Z2019-03-27T01:25:21ZS-EPMC12658081622758110.1128/mcb.25.21.9292-9303.200510.1128/MCB.25.21.9292-9303.2005