Abstract
Abstract Protein inhibitors of activated STATs (PIAS) represent a small family of nuclear proteins that modulate the activity of many transcription factors and act as E3 ligases for covalent modification of proteins with the small ubiquitin-like modifier (SUMO). In particular, PIASy has been shown to inhibit the activation of gene expression by the IFN-responsive transcription factor STAT1 and the Wnt-responsive transcription factor LEF1. To assess the function of PIASy in vivo, we generated and analyzed mice carrying a targeted mutation of the Piasy gene. We find that homozygous mutant mice have no obvious morphological defects and have a normal distribution of lymphocyte populations. Molecular analysis of signaling in response to IFN-γ and Wnt agonists revealed a modest reduction in the activation of endogenous and transfected target genes. Two-dimensional analysis of total proteins and SUMO-modified proteins in transformed pre-B cells showed no significant differences between wild-type mice and homozygous mutant mice. Taken together, our data indicate that PIASy has a modest effect on cytokine and Wnt signaling, suggesting a redundancy with other members of the family of PIAS proteins.
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Dates
Type | When |
---|---|
Created | 11 years, 4 months ago (April 20, 2014, 8:57 p.m.) |
Deposited | 8 months ago (Jan. 2, 2025, 1:44 p.m.) |
Indexed | 4 months, 3 weeks ago (April 10, 2025, 7:12 a.m.) |
Issued | 20 years, 9 months ago (Nov. 15, 2004) |
Published | 20 years, 9 months ago (Nov. 15, 2004) |
Published Print | 20 years, 9 months ago (Nov. 15, 2004) |
@article{Roth_2004, title={PIASy-Deficient Mice Display Modest Defects in IFN and Wnt Signaling}, volume={173}, ISSN={1550-6606}, url={http://dx.doi.org/10.4049/jimmunol.173.10.6189}, DOI={10.4049/jimmunol.173.10.6189}, number={10}, journal={The Journal of Immunology}, publisher={Oxford University Press (OUP)}, author={Roth, Wera and Sustmann, Claudio and Kieslinger, Matthias and Gilmozzi, Andrea and Irmer, Denis and Kremmer, Elisabeth and Turck, Chris and Grosschedl, Rudolf}, year={2004}, month=nov, pages={6189–6199} }