Disease relevance of PIAS3

• Here we demonstrate that PIAS3 is expressed in prostate cancer cells and its expression is induced in response to dihydrotestosterone (DHT) treatment [1].
• Overexpression of PIAS3 suppresses cell growth and restores the drug sensitivity of human lung cancer cells in association with PI3-K/Akt inactivation [2].
• Increased PIAS3 expression was observed in 100/103 samples examined in a variety of human cancers including lung, breast, prostate, colon-rectum, and brain tumors [3].
• CONCLUSIONS: End-stage HCV and ALD cirrhosis is characterized by impaired Stat3 DNA-binding possibly through up-regulation of Pias3 [4].

High impact information on PIAS3

• The recently discovered protein PIAS3 binds directly to STAT3 and blocks transcriptional activation [5].
• PIAS3 and Smad3 interact with each other at the endogenous protein level in mammalian cells and also in vitro, and the association occurs through the C-terminal domain of Smad3 [6].
• Activation of Smad transcriptional activity by protein inhibitor of activated STAT3 (PIAS3) [6].
• Furthermore, we show that PIAS3, Smad3, and p300 can form a ternary complex, which is markedly increased by TGF-beta treatment [6].
• Following cellular activation, PIAS3 is released from MITF and binds to STAT3 [7].

Biological context of PIAS3

• Downregulation of PIAS3 by RNA interference reverses its effect on TNF-alpha-mediated NF-kappaB activation [8].
• The recently discovered protein inhibitor of activated STAT3 (PIAS3) binds directly to STAT3 and blocks transcriptional activation [9].
• Ectopic overexpression of PIAS3 suppressed AR-mediated gene activation induced by DHT-stimulation in LNCaP cells [1].
• Inhibition of PIAS3 with small interfering RNA, nevertheless, led cancer cells to accelerate cell proliferation, deteriorate chemosensitivity, and augment Akt phosphorylation [2].
• Here we report the isolation and chromosome mapping of the human PIAS3 gene [10].

Anatomical context of PIAS3

• Over-expression of PIAS3 can induce apoptosis in prostate cancer cell lines both in vitro and in vivo [3].
• Checking endogenous PIAS3 expression in various human specimens by immunohistochemistry, we report that basal amounts of PIAS3 exist in the nucleus in a majority of epithelial and endothelial cells [3].
• Based on polymerase chain reaction assisted analysis of a human/rodent mono-chromosomal hybrid cell panel and a radiation hybrid mapping panel, the human PIAS3 gene was mapped to the chromosome 1q21 region [10].

Associations of PIAS3 with chemical compounds

• The interaction with MR was enhanced in the presence of aldosterone, an MR agonist, and was found to occur through a conserved, serine- and acidic amino acid residue-rich domain of PIAS3 [11].
• Our data also suggested that PIAS3 was recruited in a largely hormone-dependent manner in response to a progesterone-responsive promoter [12].

Physical interactions of PIAS3

• In co-transfection experiments, the full-length ATBF1 was found to form complexes with PIAS3 in Hep G2 cells [13].

Enzymatic interactions of PIAS3

• PIAS-3 protein was identified as a new c-Myb-specific SUMO-E3 ligase that both catalyzes conjugation of SUMO-2/3 proteins to c-Myb and exerts a negative effect on c-Myb-induced reporter gene activation [14].

Regulatory relationships of PIAS3

• In conclusion, ATBF1 can suppress the IL-6-mediated cellular response by acting together with PIAS3 [13].
• This analysis revealed that PIAS3 can inhibit MR, but not GR, transactivation in response to their corresponding ligands [11].

Other interactions of PIAS3

• Protein inhibitor of activated STAT3 (PIAS3) is a specific inhibitor of signal transducer and activator of transcription 3 (STAT3) [1].
• These results indicate that PIAS3 acts as a coregulator of AR signaling pathway in prostate cancer cells [1].
• Furthermore, we demonstrate that PIAS3 interferes with p65 binding to the CBP coactivator, thereby resulting in a decreased NF-kappaB-dependent transcription [8].
• PIAS1 and PIASxalpha but not PIAS3 or PIASxbeta enhanced the sumoylation of AR in intact cells and in vitro [15].
• PIAS3 was thus identified as an ATBF1-binding protein [13].

Analytical, diagnostic and therapeutic context of PIAS3

• In neural cells, PIAS3 exhibited a strong and specific interaction with MR, but not GR, as indicated by mammalian two-hybrid assays and co-immunoprecipitation experiments in vivo [11].

References