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

[thumbnail of TESI_SAUCHELLA.pdf]
Preview
Text
TESI_SAUCHELLA.pdf

Download (1MB) | Preview
Item Type: Tesi di dottorato
Resource language: English
Title: Integration of cAMP signaling and the ubiquitin system in the control of primary cilium
Creators:
Creators
Email
SAUCHELLA, SIMONA
simonasauchella@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:
nome
email
Avvedimento, Vittorio Enrico
vittorioenrico.avvedimento@unina.it
Tutor:
nome
email
Feliciello, Antonio
UNSPECIFIED
Date: 6 December 2017
Number of Pages: 57
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

Collection description

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.

Downloads

Downloads per month over past year

Actions (login required)

View Item View Item