A crosstalk between hSiah2 and Pias E3-ligases modulates Pias-dependent activation

Protein inhibitor of activated STAT ( Pias) and human homologues of seven in absentia ( hSiah) proteins both exhibit properties of ubiquitin- family peptides conjugating enzymes. Pias present E3- ligase activity for small ubiquitin-related modifiers ( Sumo) covalent attachment to their targets. This post- translational modi. cation is responsible for the activation of different transcription factors such as AP1. HSiah proteins possess ubiquitin- E3-ligase activity that triggers their partners to proteasomal-dependent degradation. The present study identifies Pias as a new hSiah2- interacting protein. We demonstrate that hSiah2 regulates specifically the proteasome-dependent degradation of Pias proteins. On reverse, Pias does not prevent hSiah2 degradation. We provide evidences for hSiah2- dependent degradation of Pias as being a mechanism in the regulation of c- jun N- terminal kinase- activating pathways. This report describes a new interconnection between sumoylation and ubiquitination pathways by regulating the levels of the E3-ligases available for these processes.