HGNC Approved Gene Symbol: PIAS3
Cytogenetic location: 1q21.1 Genomic coordinates (GRCh38) : 1:145,848,522-145,859,081 (from NCBI)
STAT proteins (e.g., STAT1, 600555) are latent cytoplasmic transcription factors that become activated by tyrosine phosphorylation in response to cytokine stimulation. Using PIAS1 (603566), an inhibitor of activated STAT1, for EST database searches and cDNA library screening, Chung et al. (1997) identified PIAS3, an inhibitor of activated STAT3 (102582). They found that PIAS3 has a molecular mass of about 68 kD. Ueki et al. (1999) independently isolated a PIAS3 cDNA encoding a deduced 619-amino acid protein that shares 83% sequence identity with mouse Pias3. PIAS3 also shares approximately 55% identity with PIAS1 and the PIASX proteins (603567) and 39% identity with PIASY (605989). Northern blot analysis detected wide expression of PIAS3 in human tissues.
Ueki et al. (1999) identified PIAS3 as an inhibitor of activated STAT3. Levy et al. (2002) found that PIAS3 binds microphthalmia-associated transcription factor (MITF; 156845), a key DNA-binding protein, in rat basophilic leukemia cells and mouse melanocytes. They observed direct binding of MITF by PIAS3 in coimmunoprecipitation and in vitro pull-down assays. Gel-shift assays showed that PIAS3 can block MITF DNA-binding activity, and cotransfection of MITF and PIAS3 in NIH 3T3 cells inhibited MITF-driven transcription activity. Interaction between PIAS3 and MITF was independent of STAT3 binding.
Using somatic cell hybrid and radiation hybrid analysis, Ueki et al. (1999) mapped the PIAS3 gene to chromosome 1q21.
Chung, C. D., Liao, J., Liu, B., Rao, X., Jay, P., Berta, P., Shuai, K. Specific inhibition of Stat3 signal transduction by PIAS3. Science 278: 1803-1805, 1997. [PubMed: 9388184] [Full Text: https://doi.org/10.1126/science.278.5344.1803]
Levy, C., Nechushtan, H., Razin, E. A new role for the STAT3 inhibitor, PIAS3: a repressor of microphthalmia transcription factor. J. Biol. Chem. 277: 1962-1966, 2002. [PubMed: 11709556] [Full Text: https://doi.org/10.1074/jbc.M109236200]
Ueki, N., Seki, N., Yano, K., Saito, T., Masuho, Y., Muramatsu, M. Isolation and chromosomal assignment of a human gene encoding protein inhibitor of activated STAT3 (PIAS3). J. Hum. Genet. 44: 193-196, 1999. [PubMed: 10319586] [Full Text: https://doi.org/10.1007/s100380050141]