Protein inhibitors of activated STAT resemble scaffold attachment factors and function as interacting nuclear receptor coregulators.
Protein inhibitor of activated STAT1 (PIAS1) functions as a nuclear receptor coregulator and is expressed in several cell types of human testis. However, the mechanism of PIAS1 coregulation is unknown. We report here that PIAS1 has characteristics of a scaffold attachment protein. PIAS1 localized in nuclei in a speckled pattern and bound A-T-rich double-stranded DNA, a function of scaffold attachment proteins in chromatin regions of active transcription. DNA binding was dependent on a 35-amino acid sequence conserved among members of the PIAS family and in scaffold attachment proteins. The PIAS family also bound the androgen receptor DNA binding domain, and binding required the second zinc finger of this domain. PIAS1 contained an intrinsic activation domain but had bi-directional effects on androgen receptor transactivation; lower expression levels inhibited and higher levels increased transactivation in CV1 cells. Other PIAS family members also had dose-dependent effects on transactivation, but they were in a direction opposite to those of PIAS1. When coexpressed with PIAS1, other PIAS family members counteracted PIAS1 coregulation of androgen receptor transactivation. The interaction of PIAS1 with other members of the PIAS family suggests a transcription coregulatory mechanism involving a multicomponent PIAS nuclear scaffold.
Tan
Jiann-An
JA
Laboratories for Reproductive Biology, Department of Pediatrics, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599-7500, USA.
Hall
Susan H
SH
Hamil
Katherine G
KG
Grossman
Gail
G
Petrusz
Peter
P
French
Frank S
FS
D000367:Age Factors; D000595:Amino Acid Sequence; D000818:Animals; D015152:Blotting, Northern; D019556:COS Cells; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism*; D004247:DNA / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008156:Luciferases / Q000378:metabolism; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D010957:Plasmids / Q000378:metabolism; D011485:Protein Binding; D050828:Protein Inhibitors of Activated STAT; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000378:metabolism* / Q000502:physiology*; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D013737:Testis / Q000378:metabolism; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D014162:Transfection; D020798:Two-Hybrid System Techniques; D001616:beta-Galactosidase / Q000378:metabolism
D016376:Oligonucleotides, Antisense; C494211:Pias1 protein, mouse; D050828:Protein Inhibitors of Activated STAT; D011506:Proteins; D011944:Receptors, Androgen; D004247:DNA; D008156:Luciferases; D001616:beta-Galactosidase