Activation of p53 by protein inhibitor of activated Stat1 (PIAS1).
The tumor suppressor protein p53 functions as a transcriptional factor that activates genes controlling cell cycle arrest and apoptosis. Here, we report that protein inhibitor of activated Stat1 (PIAS1) interacts with the tetramerization and C-terminal regulatory domains of p53 in yeast two-hybrid analyses. Endogenous PIAS1 is also associated with endogenous p53 in mammalian cells. Ectopic expression of PIAS1 activates p53-mediated expression in mouse embryonic fibroblast cells (p53(-/-)) as well as a variety of other cell lines. Furthermore, ectopic expression of PIAS1 induces p53-mediated expression of cyclin-dependent kinase inhibitor p21 and G(1) arrest of the cell cycle in H1299 cells. In addition, a PIAS1 mutant without the RING-finger domain required for sumoylation could still activate p53-mediated gene expression, indicating that activation of p53 by PIAS1 does not require the RING-finger domain. Taken together, our results suggest that PIAS1 is a novel activator of p53.
Megidish
Tamar
T
Molecular Pharmacology Program, Sloan-Kettering Institute, Cornell University, New York, New York 10021, USA.
Xu
Juliana H
JH
Xu
C Wilson
CW
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D002453:Cell Cycle; D002460:Cell Line; D002478:Cells, Cultured; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000378:metabolism; D018076:DNA, Complementary / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D016193:G1 Phase; D017930:Genes, Reporter; D016158:Genes, p53 / Q000235:genetics; D019298:Glucose-6-Phosphate / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D008156:Luciferases / Q000378:metabolism; D051379:Mice; D010957:Plasmids / Q000378:metabolism; D011233:Precipitin Tests; D011485:Protein Binding; D050828:Protein Inhibitors of Activated STAT; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism*; D014158:Transcription, Genetic; D014162:Transfection; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D020798:Two-Hybrid System Techniques
C493956:CDKN1A protein, human; C493957:Cdkn1a protein, mouse; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D018076:DNA, Complementary; C494211:Pias1 protein, mouse; D050828:Protein Inhibitors of Activated STAT; D011506:Proteins; D016159:Tumor Suppressor Protein p53; D019298:Glucose-6-Phosphate; D000255:Adenosine Triphosphate; D008156:Luciferases