Delle Donne, Rossella (2015) Ubiquitin-dependent control of Kinase Suppressor of Ras 1 (KSR1) signaling by the RING ligase praja2. [Tesi di dottorato]


Download (10MB) | Preview
[error in script] [error in script]
Item Type: Tesi di dottorato
Resource language: English
Title: Ubiquitin-dependent control of Kinase Suppressor of Ras 1 (KSR1) signaling by the RING ligase praja2.
Delle Donne,
Date: 30 March 2015
Number of Pages: 77
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: 27
Coordinatore del Corso di dottorato:
Avvedimento, Vittorio
Feliciello, AntonioUNSPECIFIED
Date: 30 March 2015
Number of Pages: 77
Keywords: KSR1, praja2, ubiquitination
Settori scientifico-disciplinari del MIUR: Area 05 - Scienze biologiche > BIO/11 - Biologia molecolare
Area 06 - Scienze mediche > MED/04 - Patologia generale
Date Deposited: 09 Apr 2015 09:51
Last Modified: 07 May 2016 01:00
DOI: 10.6092/UNINA/FEDOA/10272

Collection description

Kinase Suppressor of Ras 1 (KSR1) is an evolutionally conserved protein kinase that plays a fundamental role in mitogenic pathway. In response to Ras activation, KSR1 assembles a tripartite kinase complex that optimally transfers signals generated at cell membrane to downstream ERK signaling. The role of KSR1 in Ras signaling has been largely explored. However, the impact of attenuating signals on KSR1 was still elusive. Here, I contributed to identify a novel mechanism of ERK attenuation based on the ubiquitin-dependent control of KSR1. Stimulation of membrane receptors by growth factor induced a rapid poly-ubiquitination of KSR1, which paralleled the decay of ERK signaling. We identified praja2 as the principal E3 ligase that ubiquitinates KSR1. Interfering with praja2 expression or activity impeded KSR1 ubiquitination and sustained ERK signaling. Thus, the dynamic interplay between the ubiquitin system and scaffold components of the Ras pathway contributes to shape the profile of ERK signaling, profoundly impacting on fundamental aspects of cell behavior.


Downloads per month over past year

Actions (login required)

View Item View Item