A20 deubiquitinase controls PGC-1a expression in the adipose tissue

Author(s)

Bruna Bombassaro

• Document type: Master's Dissertation
• Press: Campinas, SP.
• Institution: Universidade Estadual de Campinas (UNICAMP). Faculdade de Ciências Médicas
• Defense date: 2013-04-22

Examining board members

Licio Augusto Velloso; Silvana Bordin; Marcio Alberto Torsoni

• Advisor: Licio Augusto Velloso

Abstract

Peroxisome proliferator-activated receptor ? coactivator 1 alpha (PGC-1?) plays an important role in whole body metabolism and, particularly in glucose homeostasis. Its expression is tightly regulated and, small variations in tissue levels can have a major impact in a number of physiological and pathological conditions. Recent studies have shown that the ubiquitin/proteasome system plays a role in the control of PGC-1? degradation. Here we evaluated the interaction of PGC-1? with the protein A20, which plays a dual-role in the control of the ubiquitin/proteasome system acting as a deubiquitinase and as an E3 ligase. We employed immunoprecipitation, quantitative real-time PCR and immunofluorescence staining to evaluate PGC-1?, A20, PPAR? and ubiquitin in the adipose tissue of humans and mice. Our results show that, in distinct sites of the adipose tissue A20 binds to PGC-1?. At least in the subcutaneous fat of humans and mice the levels of PGC-1? decrease during obesity, while its physical association with A20 increases. The inhibition of A20 leads to a reduction of PGC-1? and PPAR? expression, suggesting that A20 acts as a protective factor against PGC-1? disposal. Thus, we provide evidence that mechanisms regulating PGC-1? ubiquitination are potentially involved in the control of the function of this transcriptional co-activator (AU)

• FAPESP's process: 10/13210-5 - Evaluation of the involvement of A20 deubiquitinase in the inflamation control in obesy adipose tissue
• Grantee: Bruna Bombassaro
• Support Opportunities: Scholarships in Brazil - Master