Rinaldi, Laura (2016) Control of PKA signaling by the Ubiquitin proteasome system (UPS). [Tesi di dottorato]

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Tipologia del documento: Tesi di dottorato
Lingua: English
Titolo: Control of PKA signaling by the Ubiquitin proteasome system (UPS)
Rinaldi, Lauralaurarinaldi2000@yahoo.it
Data: 30 Marzo 2016
Numero di pagine: 59
Istituzione: Università degli Studi di Napoli Federico II
Dipartimento: Medicina Molecolare e Biotecnologie Mediche
Scuola di dottorato: Medicina molecolare
Dottorato: Patologia e fisiopatologia molecolare
Ciclo di dottorato: 28
Coordinatore del Corso di dottorato:
Avvedimento, Vittorio Enricovittorioenrico.avvedimento@unina.it
Feliciello, Antonio[non definito]
Data: 30 Marzo 2016
Numero di pagine: 59
Parole chiave: cAMP, ubiquitin proteasome system, PKA
Settori scientifico-disciplinari del MIUR: Area 06 - Scienze mediche > MED/04 - Patologia generale
Depositato il: 13 Apr 2016 10:28
Ultima modifica: 05 Mag 2018 01:00
URI: http://www.fedoa.unina.it/id/eprint/10840
DOI: 10.6093/UNINA/FEDOA/10840


Stimulation of G protein coupled receptors(GPCRs) causes the increase of cAMP intracellular levels. The main effector of cAMP signaling is Protein kinase A (PKA), which, in its inactive form, is constituted by two catalytic (Cs) and two regulatory (Rs) subunits. The binding of cAMP to the Rs causes the disassembly of the holoenzyme and the release of the Cs in the cytoplasm, with the consequent phosphorylation of a wide array of cellular substrates. The duration and the amplitude of the PKA signaling is dependent on the amount of free C subunits in the cell. Here I contributed to identify a novel mechanism of PKA signaling attenuation, based on the ubiquitination and degradation of the C subunit of PKA (PKA-C). Stimulation of GPCRs induced poly-ubiquitination and degradation of PKA-C , causing the decrease of PKA substrates activation. I identified the complex HSP70/CHIP as responsible for this ubiquitination. Interfering with CHIP expression or inhibiting the HSP70 activity inhibited PKA-C ubiquitination and sustained PKA signaling. Thus the HSP70/CHIP complex regulates the total concentration of C subunits, tuning the strength and duration of PKA signaling in response to cAMP.

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