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

p27(Kip1) is an inhibitor of a broad spectrum of cyclin-dependent kinases (CDKs), and the loss of a single p27(Kip1) allele is thereby sufficient to increase tumor incidence via CDK-mediated cell cycle entry. As such, down-regulation of p27(Kip1) protein levels, in particular nuclear expressed p27(Kip1), is implicated in both disease progression and poor prognosis in a variety of cancers. p27(Kip1) expression is positively regulated by the transcription factor MENIN, and inhibited by oncogenic transcription factors MYC and PIM. However, regulation of p27(Kip1) protein expression and function is predominantly through post-translational modifications that alter both the cellular localization and the extent of E3 ubiquitin ligase-mediated degradation. Phosphorylation of p27(Kip1) at Thr(187) and Ser(10) is a prerequisite for its degradation via the E3 ubiquitin ligases SKP2 (nuclear) and KPC (cytoplasmic), respectively. Additionally, Ser(10) phosphorylated p27(Kip1) is predominantly localized in the cytoplasm due to the nuclear export protein CRM1. Another E3 ubiquitin ligase, PIRH2, degrades p27(Kip1) in both the cytoplasm and nucleus independent of phosphorylation state. As such, inhibition of cell cycle entry and progression in a variety of cancers may be achieved with therapies designed to correct p27(Kip1) localization and/or block its degradation.
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PMID:p27(Kip1) signaling: Transcriptional and post-translational regulation. 2627 44

The aim of this study was to analyze the metabolome of several Klebsiella pneumoniae strains characterized by different resistance patterns. A total of 59 bacterial strains (27 carbapenemase-negative and 32 carbapenemase-positive) were included and their metabolic features were assessed in basal conditions. Moreover, 8 isolates (4 wild-type and 4 KPC-producers) were randomly selected to evaluate the impact of sub-lethal concentrations of meropenem on bacterial metabolism. The metabolomic analysis was performed by 1H-NMR spectroscopy both on filtered supernatants and cell lysates. A total of 40 and 20 molecules were quantified in the intracellular and the extracellular metabolome, respectively. While in basal conditions only five metabolites showed significant differences between carbapenemase-positive and negative strains, the use of meropenem had a profound impact on the whole bacterial metabolism. In the intracellular compartment, a reduction of different overflow metabolites and organic acids (e.g. formate, acetate, isobutyrate) was noticed, whereas, in the extracellular metabolome, the levels of several organic acids (e.g. succinate, acetate, formate, lactate) and amino acids (aspartate, threonine, lysine, alanine) were modified by meropenem stimulation. Interestingly, carbapenemase-positive and negative strains reacted differently to meropenem in terms of number and type of perturbed metabolites. In wild-type strains, meropenem had great impact on the metabolic pathways related to methane metabolism and alanine, aspartate and glutamate metabolism, whereas in KPC-producers the effect was predominant on pyruvate metabolism. The knowledge about the bacterial metabolic profiles could help to set up innovative diagnostic methods and new antimicrobial strategies to fight the global crisis against carbapenemase-positive K. pneumoniae.
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PMID:Impact of meropenem on Klebsiella pneumoniae metabolism. 3044 48

HOX proteins are homeodomain transcription factors critically involved in patterning animal embryos and controlling organogenesis. While the functions of HOX proteins and the processes under their control begin to be well documented, the modalities of HOX protein activity regulation remain poorly understood. Here we show that HOXA2 interacts with PPP1CB, a catalytic subunit of the Ser/Thr PP1 phosphatase complex. This interaction co-localizes in the cytoplasm with a previously described HOXA2 interactor, KPC2, which belongs to the KPC E3 ubiquitin ligase complex. We provide evidence that HOXA2, PPP1CB and KPC2 define a molecularly and functionally interacting complex. Collectively, our experiments support that PPP1CB and KPC2 together inhibit the activity of HOXA2 by activating its nuclear export, but favored HOXA2 de-ubiquitination and stabilization thereby establishing a store of HOXA2 in the cytoplasm.
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PMID:HOXA2 activity regulation by cytoplasmic relocation, protein stabilization and post-translational modification. 3132 36