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• W2078633558 abstract "<i>Background/Aim:</i> Protein kinase C (PKC) is a family of isoenzymes playing a key role in the regulation of gonadotrope cell functions. Specific PKC isoforms are activated and downregulated differentially by gonadotropin-releasing hormone (GnRH) and the phorbol ester TPA. In the present study, focusing mainly on PKC ε, the mechanisms underlying the proteasome-dependent downregulation of GnRH-activated PKC ε and TPA-sensitive PKC α and ε isoenzymes were investigated in αT3-1 gonadotrope cells. <i>Methods/Results:</i> In pull-down assays involving the use of glutathione-agarose affinity beads conjugated with a GST-fusion protein containing ubiquitin-associated domains of Rad23 that bind very likely to K48-linked polyubiquitinated proteins, TPA induced rapid (within 15 min) and sustained (up to 4 h) PKC α and PKC ε polyubiquitination. However, GnRH selectively elicited receptor-dependent polyubiquitination of PKC ε, but not that of PKC α. The GnRH-evoked PKC ε polyubiquitination was a strong, fast process (taking place as early as 10 min) which decreased progressively with time (but was still detectable after 4 h of treatment). In addition, no apparent association between PKC ε and the lysosomal compartment was observed upon performing double-labeling immunofluorescence and confocal microscopy, after either 10 min or 1 hour of stimulation by GnRH or the phorbol ester. <i>Conclusion:</i> In αT3-1 gonadotrope cells, polyubiquitination is therefore the event triggering GnRH-evoked PKC ε desensitization as well as TPA-induced PKC α and PKC ε downregulations; it precedes the respective isoenzyme’s degradation by the proteasome complex." @default.
• W2078633558 created "2016-06-24" @default.
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• W2078633558 date "2008-10-16" @default.
• W2078633558 modified "2023-10-18" @default.
• W2078633558 title "Ubiquitination as a Priming Process of PKC αand PKC ε Degradation in the αT3-1 Gonadotrope Cell Line" @default.
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• W2078633558 doi "https://doi.org/10.1159/000164694" @default.
• W2078633558 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/18931473" @default.
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