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HGNC Approved Gene Symbol: PIAS2
Cytogenetic location: 18q21.1 Genomic coordinates (GRCh38): 18:46,803,218-46,920,145 (from NCBI)
STAT proteins (e.g., STAT1, 600555) are latent cytoplasmic transcription factors that become activated by tyrosine phosphorylation in response to cytokine stimulation. By searching an EST database and by cDNA library screening, Liu et al. (1998) identified cDNAs encoding PIASX and several other mammalian proteins related to PIAS1 (protein inhibitor of activated STAT1; 603566). The authors found that the PIASX transcript is alternatively spliced to yield 2 protein isoforms, PIASX-alpha and PIASX-beta, that differ in their C-terminal regions. Like other members of the PIAS family, the predicted PIASX proteins contain a putative zinc-binding motif and a highly acidic region.
Tussie-Luna et al. (2002) reported that mouse Piasx-beta has an N-terminal SAP domain, followed by a proline-rich region, a RING-like zinc finger domain, 2 nuclear localization signals, and a serine/threonine-rich C-terminal domain. Mouse Piasx-beta localized in the nucleus.
Tussie-Luna et al. (2002) found that mouse Piasx-beta interacted with both TFII-I (GTF2I; 601679), a transcriptional activator, and MUSTRD1 (GTF2IRD1; 604318), a transcriptional repressor. Binding of Piasx-beta to TFII-I augmented TFII-I transcriptional activity. Piasx-beta-TFII-I interaction could be titrated out by MUSTRD1, leading to transcriptional repression of TFII-I-dependent promoters.
Yang and Sharrocks (2006) identified human PIASX-alpha as a key regulator that determines the differential response of the transcription factor ELK1 (311040) to activation of the ERK (see MAPK3; 601795) or stress-activated p38 MAP kinase (MAPK14; 600289) pathways. In response to ERK pathway activation, PIASX-alpha functioned as a coactivator to facilitate removal of SUMO (see 601912) and HDAC2 (605164) from ELK1. PIASX-alpha acted in the opposite manner, inhibiting loss of SUMO and HDAC2 from ELK1, in response to p38 MAP kinase pathway activation. Phosphorylation of PIASX-alpha through the p38 MAP kinase pathway allowed it to switch between these alternative functions.
The International Radiation Hybrid Mapping Consortium mapped the PIASX gene to chromosome 18q12.1-q12.3 (sts-H25373).
Liu, B., Liao, J., Rao, X., Kushner, S. A., Chung, C. D., Chang, D. D., Shuai, K. Inhibition of Stat1-mediated gene activation by PIAS1. Proc. Nat. Acad. Sci. 95: 10626-10631, 1998. [PubMed: 9724754] [Full Text: https://doi.org/10.1073/pnas.95.18.10626]
Tussie-Luna, M. I., Michel, B., Hakre, S., Roy, A. L. The SUMO ubiquitin-protein isopeptide ligase family member Miz1/PIASx-beta/Siz2 is a transcriptional cofactor for TFII-I. J. Biol. Chem. 277: 43185-43193, 2002. [PubMed: 12193603] [Full Text: https://doi.org/10.1074/jbc.M207635200]
Yang, S.-H., Sharrocks, A. D. PIASx-alpha differentially regulates the amplitudes of transcriptional responses following activation of the ERK and p38 MAPK pathways. Molec. Cell 22: 477-487, 2006. [PubMed: 16713578] [Full Text: https://doi.org/10.1016/j.molcel.2006.03.037]