PIASy-deficient mice display modest defects in IFN and Wnt signaling.
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-gamma 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.
Roth
Wera
W
Gene Center and Institute of Biochemistry, University of Munich, Munich, Germany.
Sustmann
Claudio
C
Kieslinger
Matthias
M
Gilmozzi
Andrea
A
Irmer
Denis
D
Kremmer
Elisabeth
E
Turck
Chris
C
Grosschedl
Rudolf
R
D000818:Animals; D002461:Cell Line, Transformed; D002478:Cells, Cultured; D016207:Cytokines / Q000502:physiology; D015180:Electrophoresis, Gel, Two-Dimensional; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D020868:Gene Silencing; D006410:Hematopoiesis / Q000235:genetics / Q000276:immunology; D006720:Homozygote; D007371:Interferon-gamma / Q000494:pharmacology; D007372:Interferons / Q000502:physiology*; D047908:Intracellular Signaling Peptides and Proteins / Q000172:deficiency* / Q000235:genetics* / Q000502:physiology; D007763:Lac Operon; D051379:Mice; D018345:Mice, Knockout; D016254:Mutagenesis, Insertional / Q000379:methods; D050828:Protein Inhibitors of Activated STAT; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D015398:Signal Transduction / Q000235:genetics* / Q000276:immunology; D051153:Wnt Proteins
D016207:Cytokines; D047908:Intracellular Signaling Peptides and Proteins; C414349:Piasy protein, mouse; D050828:Protein Inhibitors of Activated STAT; D011518:Proto-Oncogene Proteins; D051153:Wnt Proteins; D007371:Interferon-gamma; D007372:Interferons