Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C1855645 (KPC)
 1,473 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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 KPC2 derivative lacking the STI1 domain was greatly impaired in this regard. Depletion of KPC2 by RNA interference resulted in inhibition of p27 degradation at the G(1) phase, and introduction of KPC2 derivatives into the KPC2-depleted cells revealed that the NH(2)-terminal UBA domain of KPC2 is essential for p27 degradation. These observations suggest that KPC2 cooperatively regulates p27 degradation with KPC1 and that the STI1 domain as well as the UBL and UBA domains of KPC2 are indispensable for its function.
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PMID:Role of the UBL-UBA protein KPC2 in degradation of p27 at G1 phase of the cell cycle. 1622 81

Antibiotic resistance associated with the clinically significant carbapenemases KPC, NDM and OXA-48 in Enterobacteriaceae is emerging as worldwide. In Australia, IMP-producing Enterobacteriaceae are the most prevalent carbapenemase-producing Enterobacteriaceae (CPE). Genomic characteristics of such CPE are well described, but the corresponding proteome is poorly characterised. We have thus developed a method to analyse dynamic changes in the proteome of CPE under antibiotic pressure. Specifically, we have investigated the effect of meropenem at sub-lethal concentrations to develop a better understanding of how antibiotic pressure leads to resistance. Escherichia coli strains producing either NDM-, IMP- or KPC-type carbapenemases were included in this study, and their proteomes were analysed in growth conditions with or without meropenem. The most significant difference in the bacterial proteomes upon the addition of meropenem was triggered amongst NDM-producers and to a lower extent amongst KPC-producers. In particular, HU DNA-binding proteins, the GroEL/GroES chaperonin complex and GrpE proteins were overexpressed. These proteins may thus contribute to the better adaptability of NDM- and KPC-producers to meropenem. A significant meropenem-induced increase in the expression of the outer membrane protein A was only observed in IMP-producers, thus demonstrating that carbapenemase-mediated resistance relies on far more complex mechanisms than simple inactivation of the antibiotic.
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PMID:The use of SWATH to analyse the dynamic changes of bacterial proteome of carbapanemase-producing Escherichia coli under antibiotic pressure. 2949 67