SUMO-E3 ligase PIAS4 regulates tau stability and promotes its phosphorylation

LIBERMAN, ANA CLARA; BUDZIÑSKI, MAIA LUDMILA; SENIN, SERGIO; SOKN, CLARA; ARZT, EDUARDO; GOBBINI, ROMINA

Mar del Plata

Congreso; XXXII CONGRESO ANUAL SAN 2017; 2017

Sociedad Argentina de Investigación en Neurociencias

Tau is a microtubule-associated protein expressed mainly in neurons which plays a key role in regulating tubulin dynamics, axonal transport and axonal growth. Tau deregulation leads to neurodegenerative diseases known as tauopathies which are characterized by the formation of intracellular deposits of hyperphosphorylated tau. Hsp90 is a major cellular chaperone which assembles large complexes with a variety of co-chaperones like the immunophilin FKBP51. The Hsp90/FKBP51 complex has been described as a potential enhancer of abnormal tau stability, by inhibiting its proteosomal degradation. Our group has recently demonstrated that FKBP51 SUMOylation is necessary in order to form this complex, and that PIAS4 is its specific SUMO E3 ligase. Taking this into consideration we propose to study the role of PIAS4 on tau?s function. Our preliminary results suggest that PIAS4 promotes tau and phospho-tau accumulation, increasing tau stability probably by inhibiting it´s degradation by the ubiquitin-proteasome system. PIAS4 effect over tau protein is dependent on PIAS4 E3 ligase activity and FKBP51 SUMOylation.