Rinaldi, Laura (2016) Control of PKA signaling by the Ubiquitin proteasome system (UPS). [Tesi di dottorato]
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| Item Type: | Tesi di dottorato |
|---|---|
| Resource language: | English |
| Title: | Control of PKA signaling by the Ubiquitin proteasome system (UPS) |
| Creators: | Creators Email Rinaldi, Laura laurarinaldi2000@yahoo.it |
| Date: | 30 March 2016 |
| Number of Pages: | 59 |
| Institution: | Università degli Studi di Napoli Federico II |
| Department: | Medicina Molecolare e Biotecnologie Mediche |
| Scuola di dottorato: | Medicina molecolare |
| Dottorato: | Patologia e fisiopatologia molecolare |
| Ciclo di dottorato: | 28 |
| Coordinatore del Corso di dottorato: | nome email Avvedimento, Vittorio Enrico vittorioenrico.avvedimento@unina.it |
| Tutor: | nome email Feliciello, Antonio UNSPECIFIED |
| Date: | 30 March 2016 |
| Number of Pages: | 59 |
| Keywords: | cAMP, ubiquitin proteasome system, PKA |
| Settori scientifico-disciplinari del MIUR: | Area 06 - Scienze mediche > MED/04 - Patologia generale |
| Date Deposited: | 13 Apr 2016 10:28 |
| Last Modified: | 05 May 2018 01:00 |
| URI: | http://www.fedoa.unina.it/id/eprint/10840 |
| DOI: | 10.6093/UNINA/FEDOA/10840 |
Collection description
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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