SAUCHELLA, SIMONA
(2017)
Integration of cAMP signaling and the ubiquitin system in the control of primary cilium.
[Tesi di dottorato]
| Item Type: |
Tesi di dottorato
|
| Lingua: |
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 |
| Uncontrolled Keywords: |
ciliogenesis, cAMP, ubiquitylation |
| Settori scientifico-disciplinari del MIUR: |
Area 06 - Scienze mediche > MED/04 - Patologia generale |
[error in script]
[error in script]
| 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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