title: Protein inhibitor of activated STAT Y (PIASy) and a splice variant lacking exon 6 enhance sumoylation but are not essential for embryogenesis and adult life.
abstract: Protein inhibitor of activated STAT Y (PIASy) is the shortest member of the PIAS family and has been reported to modulate the transcriptional activities of STAT1, lymphoid enhancer factor 1 (LEF-1), and the androgen receptor. PIAS proteins have also been identified as E3 ligases for the small ubiquitin-like modifier (SUMO) proteins. PIASy in particular has been reported to mediate SUMO-2/3 modification of LEF-1, sequestering it into nuclear bodies, and SUMO-1 ligation to c-Myb, modulating its transcriptional activation properties. We have cloned murine Piasy and a splice variant which omits exon 6, containing the nuclear retention PINIT motif. Cell culture studies indicate that both the full length and the splice variant are localized in the nucleus but differentially enhance SUMO ligation. To further understand the functions of PIASy, we have generated PIASy-deficient mice. Surprisingly, Piasy(-/-) mice appear phenotypically normal. Activation of STAT1 is not significantly perturbed in Piasy(-/-) cells, and sumoylation patterns for SUMO-1 or SUMO-3 modification are similar when comparing tissues and embryonic fibroblasts from wild-type and knockout mice. Our study demonstrates that at steady state, PIASy is either dispensable or compensated for by other PIAS family members or by other mechanisms when deleted.
authors.affiliation: Molecular and Medical Pharmacology, Howard Hughes Medical Institute, University of California, Los Angeles, 90095, USA.
authors.forename: Kelly A
authors.initials: KA
authors.lastname: Wong
authors.forename: Rachel
authors.initials: R
authors.lastname: Kim
authors.forename: Heather
authors.initials: H
authors.lastname: Christofk
authors.forename: Jing
authors.initials: J
authors.lastname: Gao
authors.forename: Gregory
authors.initials: G
authors.lastname: Lawson
authors.forename: Hong
authors.initials: H
authors.lastname: Wu
mesh_terms: D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics* / Q000502:physiology*; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000378:metabolism; D005314:Embryonic and Fetal Development / Q000235:genetics / Q000502:physiology; D005091:Exons; D005260:Female; D018390:Gene Targeting; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D008979:Moloney murine leukemia virus / Q000235:genetics / Q000472:pathogenicity / Q000502:physiology; D010641:Phenotype; D050828:Protein Inhibitors of Activated STAT; D050794:STAT1 Transcription Factor; D025842:SUMO-1 Protein / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D025841:Small Ubiquitin-Related Modifier Proteins / Q000378:metabolism*; D015534:Trans-Activators / Q000378:metabolism; D014452:Ubiquitins / Q000378:metabolism; D014779:Virus Replication / Q000502:physiology
chemical_list: D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; C414349:Piasy protein, mouse; D050828:Protein Inhibitors of Activated STAT; D050794:STAT1 Transcription Factor; D025842:SUMO-1 Protein; D025841:Small Ubiquitin-Related Modifier Proteins; C494080:Stat1 protein, mouse; C117908:Sumo3 protein, mouse; D015534:Trans-Activators; D014452:Ubiquitins