The PIAS (protein inhibitor of activated STAT) proteins play a crucial role as transcriptional coregulators in various cellular pathways, including the STAT, p53 and the steroid hormone signaling pathway. The PIAS protein family includes at least five evolutionarily conserved genes, including PIAS3. The major function of the PIAS proteins is the control of gene transcription and can also act as small ubiquitin-like-modifier (SUMO) E3 ligases. PIAS3 binds specifically to STAT3 following the stimulation of STAT3. Increased expression of PIAS3 has been observed in several human cancers, including lung, breast, and brain tumors, but not in anaplastic lymphoma kinase-positive T/null-cell lymphomas, indicating that PIAS3 plays multiple roles in different tissue and cell types.