Journal article
Multifunctional Role of the Pitx2 Homeodomain Protein C-Terminal Tail
Molecular and cellular biology, Vol.19(10), pp.7001-7010
10/1999
DOI: 10.1128/MCB.19.10.7001
PMCID: PMC84695
PMID: 10490637
Abstract
Pitx2 is a newly described bicoid-like homeodomain transcription factor that is defective in Rieger syndrome and shows a striking leftward developmental asymmetry. We have previously shown that Pitx2 (also called Ptx2 and RIEG) transactivates a reporter gene containing a
bicoid
enhancer and synergistically transactivates the prolactin promoter in the presence of the POU homeodomain protein Pit-1. In this report, we focused on the C-terminal region which is mutated in some Rieger patients and contains a highly conserved 14-amino-acid element. Deletion analysis of Pitx2 revealed that the C-terminal 39-amino-acid tail represses DNA binding activity and is required for Pitx2-Pit-1 interaction and Pit-1 synergism. Pit-1 interaction with the Pitx2 C terminus masks the inhibitory effect and promotes increased DNA binding activity. Interestingly, cotransfection of an expression vector encoding the C-terminal 39 amino acids of Pitx2 specifically inhibits Pitx2 transactivation activity. In contrast, the C-terminal 39-amino-acid peptide interacts with Pitx2 to increase its DNA binding activity. These data suggest that the C-terminal tail intrinsically inhibits the Pitx2 protein and that this inhibition can be overcome by interaction with other transcription factors to allow activation during development.
Details
- Title: Subtitle
- Multifunctional Role of the Pitx2 Homeodomain Protein C-Terminal Tail
- Creators
- Brad A Amendt - Department of Physiology and Biophysics, University of Iowa, Iowa City, Iowa 52242Lillian B Sutherland - Department of Physiology and Biophysics, University of Iowa, Iowa City, Iowa 52242Andrew F Russo - Department of Physiology and Biophysics, University of Iowa, Iowa City, Iowa 52242
- Resource Type
- Journal article
- Publication Details
- Molecular and cellular biology, Vol.19(10), pp.7001-7010
- DOI
- 10.1128/MCB.19.10.7001
- PMID
- 10490637
- PMCID
- PMC84695
- NLM abbreviation
- Mol Cell Biol
- ISSN
- 0270-7306
- eISSN
- 1098-5549
- Publisher
- American Society for Microbiology
- Language
- English
- Date published
- 10/1999
- Academic Unit
- Neurology; Orthodontics; Molecular Physiology and Biophysics; Anatomy and Cell Biology; Iowa Neuroscience Institute; Craniofacial Anomalies Research Center; Dental Research
- Record Identifier
- 9984020718302771
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