PIAS4 SUMO E3 ligase modulates tau and phospho-tau levels

GOBBINI, ROMINA PAULA; ARZT, EDUARDO; BUDZINSKI, MAIA LUDMILA; LIBERMAN, ANA CLARA; SOKN, MARÍA CLARA; SENIN, SERGIO

Ciudad de Buenos Aires

Simposio; Frontiers in Bioscience 3; 2018

Instituto de Investigación en Biomedicina de Buenos Aires (IBioBA, CONICET ? Partner Institute of the Max Planck Society)

Over the past few years, SUMO conjugation has been increasingly related with neurological diseases associated with abnormal protein accumulations. In particular, some of the PIAS SUMO-E3 ligases are directly linked to these processes. These E3 ligases can regulate protein-protein interactions, intracellular trafficking as well as aggregation and degradation of key neuronal substrates, therefore the dysregulation of their activity is linked to neurodegeneration. Among the different neurodegenerative diseases, tauopathies are characterized by the formation of intracellular tau deposits. These aggregates are composed mainly of hyperphosphorylated tau, but also some other modified tau species such as ubiquitinated and SUMOylated tau. SUMOylation of tau proteins may contribute to changes in protein solubility and proteolytic processing. However, the intrinsic molecular mechanism and its physiological relevance is still under investigation. In this work we evaluated the ability of the PIAS family members (PIAS1, PIAS2a, PIAS2b, PIAS3 and PIAS4) to modulate total and phospho-tau intracellular levels. We found 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.