PIAS3 is an E3-type small ubiquitin-like modifier (SUMO) ligases, stabilising the interaction between UBE2I and Ubc9 respectively and the substrate, and as a SUMO-tethering factor. It plays a crucial role as a transcriptional coregulation in various cellular pathways, including the STAT pathway and the steroid hormone signaling pathway [, , , ].PIAS3 sumoylates CCAR2, promoting its interaction with SIRT1 []and diminishes the sumoylation of ZFHX3 by preventing the colocalization of ZFHX3 with SUMO1 in the nucleus [].SUMO proteins are ubiquitin like proteins that are covalently attached to and detached from other proteins in cells to modify their function. SUMO is first activated in an ATP-dependent reaction by formation of a thioester bond with an E1 (SUMO-activating) enzyme and then transferred to the SUMO conjugating (E2) enzyme Ubc9. Ubc9 catalyses the formation of an isopeptide bond between the C-terminal of SUMO and the amino group of lysine in the target protein. Sumoylated proteins can be targeted for different cellular processes, such as nuclear transport, transcriptional regulation, apoptosis, and protein stability [].
