SAUCHELLA, SIMONA (2017) Integration of cAMP signaling and the ubiquitin system in the control of primary cilium. [Tesi di dottorato]
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| Tipologia del documento: | Tesi di dottorato |
|---|---|
| Lingua: | English |
| Titolo: | Integration of cAMP signaling and the ubiquitin system in the control of primary cilium |
| Autori: | Autore Email SAUCHELLA, SIMONA simonasauchella@hotmail.it |
| Data: | 6 Dicembre 2017 |
| Numero di pagine: | 57 |
| Istituzione: | Università degli Studi di Napoli Federico II |
| Dipartimento: | dep14 |
| Dottorato: | phd054 |
| Ciclo di dottorato: | 30 |
| Coordinatore del Corso di dottorato: | nome email Avvedimento, Vittorio Enrico vittorioenrico.avvedimento@unina.it |
| Tutor: | nome email Feliciello, Antonio [non definito] |
| Data: | 6 Dicembre 2017 |
| Numero di pagine: | 57 |
| Parole chiave: | ciliogenesis, cAMP, ubiquitylation |
| Settori scientifico-disciplinari del MIUR: | Area 06 - Scienze mediche > MED/04 - Patologia generale |
| Depositato il: | 27 Dic 2017 17:08 |
| Ultima modifica: | 11 Apr 2019 08:59 |
| URI: | http://www.fedoa.unina.it/id/eprint/12056 |
Abstract
The primary cilium is an antenna-like sensory organelle able to receive extracellular signals and it is localized on the surface of most human cells. In my thesis, I investigated the connection between G-protein coupled receptor (GPCR) signaling and the ubiquitin proteasome system (UPS) pathway in the control of cilium stability. I identified, at pericentriolar region, a trimeric complex composed by PCM1, NEK10 and PKA. I demonstrated that NEK10 has a crucial role in ciliogenesis. Phosphorylation by PKA primes NEK10 to proteasomal degradation. Disappearance of NEK10 promotes cilia resorption. I identified CHIP as the E3 ubiquitin ligase responsible of NEK10 ubiquitination and I demonstrated that CHIP mediates the effects of cAMP on primary cilium stability. Derangement of this control mechanism was observed in proliferative and genetic disorders. Collectively, the findings unveil a pericentriolar kinase signalosome that efficiently links the cAMP cascade with the ubiquitin-proteasome system, controlling essential aspects of ciliogenesis.
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