Use this URL to cite or link to this record in EThOS:
Title: Developmental profile and investigation into potential functional roles of sumoylation in brain
Author: Prado , Fernando Josa
ISNI:       0000 0004 5920 6687
Awarding Body: University of Bristol
Current Institution: University of Bristol
Date of Award: 2014
Availability of Full Text:
Access from EThOS:
Protein SUMOylation is a posttranslational modification event with various effects over its substrates, including modification of their turnover equilibrium, intracellular sorting, blocking interactions or facilitating new ones. Although most cellular SU MOylation has been linked to the nucleus and nuclear functions, in the past years an increasing number of cytosolic and membrane proteins have been reported as SUMO substrates. Compared to other modifications such ubiquitination or phosphorylation, very little is known of the role of SUMOylation in brain and its possible substrates. Also, its role in development of the central nervous system is poorly understood. In this work it is shown that levels of global SUMOylation of substrates for SUMOl and SUM02/3 decrease during development, as do most of the examined SUMOylation machinery proteins, which interestingly show an increased presence in cerebellum over the rest of the brain. PIAS3, a SUMOE3 ligase, was further characterised in brain and a new putative candidate PIAS3-PINIT-domain interactor was found : Ago2. Ago proteins are the core components of the RNA-induced silencing complexes (RISe) and mediate RNA interference. It was found that Ago2 can be SUMOylated under certain conditions, being its major acceptor site the lysine K402. Slight RNAi effect alleviation was observed in a SUMOylation-deficient mutant of Ago2. Finally I also hypothesize about a new mechanism for SUMOylation of Iysines other than the one at the consensus site. This opens an interesting avenue of research regarding the effects of SUMOylation in the RNAi pathway.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available