Journal article
Protein Inhibitors of Activated STAT (Pias1 and Piasy) Differentially Regulate Pituitary Homeobox 2 (PITX2) Transcriptional Activity
The Journal of biological chemistry, Vol.288(18), pp.12580-12595
05/03/2013
DOI: 10.1074/jbc.M112.374561
PMCID: PMC3642306
PMID: 23515314
Abstract
Background:
Protein inhibitors of activated STAT (Pias) proteins can modulate the activity of transcription factors.
Results:
Pias1 and Piasy enhance or repress pituitary homeobox 2 (PITX2) transcriptional activity.
Conclusion:
Pias interactions regulate PITX2 transcriptional activity.
Significance:
Pias proteins can differentially regulate PITX2 activity.
Protein inhibitors of activated STAT (Pias) proteins can act independent of sumoylation to modulate the activity of transcription factors and Pias proteins interacting with transcription factors can either activate or repress their activity. Pias proteins are expressed in many tissues and cells during development and we asked if Pias proteins regulated the pituitary homeobox 2 (PITX2) homeodomain protein, which modulates developmental gene expression. Piasy and Pias1 proteins are expressed during craniofacial/tooth development and directly interact and differentially regulate PITX2 transcriptional activity. Piasy and Pias1 are co-expressed in craniofacial tissues with PITX2. Yeast two-hybrid, co-immunoprecipitation and pulldown experiments demonstrate Piasy and Pias1 interactions with the PITX2 protein. Piasy interacts with the PITX2 C-terminal tail to attenuate its transcriptional activity. In contrast, Pias1 interacts with the PITX2 C-terminal tail to increase PITX2 transcriptional activity. The E3 ligase activity associated with the RING domain in Piasy is not required for the attenuation of PITX2 activity, however, the RING domain of Pias1 is required for enhanced PITX2 transcriptional activity. Bimolecular fluorescence complementation assays reveal PITX2 interactions with Piasy and Pias1 in the nucleus. Piasy represses the synergistic activation of PITX2 with interacting co-factors and Piasy represses Pias1 activation of PITX2 transcriptional activity. In contrast, Pias1 did not affect the synergistic interaction of PITX2 with transcriptional co-factors. Last, we demonstrate that Pias proteins form a complex with PITX2 and Lef-1, and PITX2 and β-catenin. Lef-1, β-catenin, and Pias interactions with PITX2 provide new molecular mechanisms for the regulation of PITX2 transcriptional activity and the activity of Pias proteins.
Details
- Title: Subtitle
- Protein Inhibitors of Activated STAT (Pias1 and Piasy) Differentially Regulate Pituitary Homeobox 2 (PITX2) Transcriptional Activity
- Creators
- Jianbo WangZhao Sun - From theZichao Zhang - From theIrfan Saadi - the Departments ofJun Wang - Texas Heart InstituteXiao Li - Anatomy and Cell Biology, andShan Gao - From theJamison J Engle - the Departments ofAdisa Kuburas - the Departments ofXueyao Fu - theWenjie Yu - Anatomy and Cell Biology, andWilliam H Klein - theAndrew F Russo - the Departments ofBrad A Amendt - Anatomy and Cell Biology, and
- Resource Type
- Journal article
- Publication Details
- The Journal of biological chemistry, Vol.288(18), pp.12580-12595
- DOI
- 10.1074/jbc.M112.374561
- PMID
- 23515314
- PMCID
- PMC3642306
- NLM abbreviation
- J Biol Chem
- ISSN
- 0021-9258
- eISSN
- 1083-351X
- Publisher
- American Society for Biochemistry and Molecular Biology; 9650 Rockville Pike, Bethesda, MD 20814, U.S.A
- Grant note
- EY011930; EY010608 / National Institutes of Health
- Alternative title
- Pias Factors Regulate PITX2 Activity
- Language
- English
- Date published
- 05/03/2013
- Academic Unit
- Neurology; Orthodontics; Molecular Physiology and Biophysics; Anatomy and Cell Biology; Iowa Neuroscience Institute; Craniofacial Anomalies Research Center; Dental Research; Internal Medicine
- Record Identifier
- 9984020765002771
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