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The catalytic unit of the proteasome and degradation of oxidized proteins

Grant number: 11/23268-3
Support type:Regular Research Grants
Duration: May 01, 2012 - April 30, 2014
Field of knowledge:Biological Sciences - Biochemistry
Principal Investigator:Marilene Demasi
Grantee:Marilene Demasi
Home Institution: Instituto Butantan. Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil


The proteasome is a proteolytic complex responsible for the degradation of intracellular proteins labeled by a poli-ubiquitin chain. It consists of a central catalytic unit named 20S proteasome (20S PT) coupled to regulatory units (19S or 11S). The 20S PT is able to degrade oxidized proteins independently on poly-ubiquitylation. The 20S PT is constituted of a central core formed by two heptameric ² rings flanked by heptameric rings termed ±. The catalytic sites are located in the ² subunits while the ±-subunits control the opening of the catalytic chamber. Among post-translational modifications of the 20S PT our group has described the S-glutathiolation of proteasomal Cys residues through reaction with glutathione. More recently our group identified those residues prone to S-glutathiolation among the 32 Cys in the yeast 20S PT. Mass spectrometry analyses of the 20S PT subunits revealed that the S-glutathiolated Cys residues are located exclusively in ±-subunits. 20S proteasomal glutathiolation promotes the opening of the catalytic chamber and increases degradation of oxidized proteins. Taken those findings into account, the goals in the present project will be: firstly to perform genomic site-specific mutations of proteasomal Cys residues prone to glutathiolation and next to evaluate the tolerance to oxidative stress, ability to remove oxidized proteins and the lifespan in the mutated cells. In parallel, to evaluate structural and functional consequences of the mutation in purified 20S PT preparations from mutated cells. (AU)

Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
DEMASI, MARILENE; SIMOES, VANESSA; BONATTO, DIEGO. Cross-talk between redox regulation and the ubiquitin-proteasome system in mammalian cell differentiation. BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS, v. 1850, n. 8, SI, p. 1594-1606, AUG 2015. Web of Science Citations: 7.

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