SAUCHELLA, SIMONA (2017) Integration of cAMP signaling and the ubiquitin system in the control of primary cilium. [Tesi di dottorato]

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Item Type: Tesi di dottorato
Lingua: English
Title: Integration of cAMP signaling and the ubiquitin system in the control of primary cilium
Creators:
CreatorsEmail
SAUCHELLA, SIMONAsimonasauchella@hotmail.it
Date: 6 December 2017
Number of Pages: 57
Institution: Università degli Studi di Napoli Federico II
Department: dep14
Dottorato: phd054
Ciclo di dottorato: 30
Coordinatore del Corso di dottorato:
nomeemail
Avvedimento, Vittorio Enricovittorioenrico.avvedimento@unina.it
Tutor:
nomeemail
Feliciello, AntonioUNSPECIFIED
Date: 6 December 2017
Number of Pages: 57
Uncontrolled Keywords: ciliogenesis, cAMP, ubiquitylation
Settori scientifico-disciplinari del MIUR: Area 06 - Scienze mediche > MED/04 - Patologia generale
Date Deposited: 27 Dec 2017 17:08
Last Modified: 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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