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Molecular and Cellular Biology, October 1999, p. 7001-7010, Vol. 19, No. 10
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Multifunctional Role of the Pitx2 Homeodomain Protein C-Terminal Tail

Brad A. Amendt,* Lillian B. Sutherland, and Andrew F. Russo

Department of Physiology and Biophysics, University of Iowa, Iowa City, Iowa 52242

Received 21 August 1998/Returned for modification 2 February 1999/Accepted 26 July 1999

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.

* Corresponding author. Present address: Department of Biological Science, The University of Tulsa, 600 S. College Ave., Tulsa, OK 74104-3189. Phone: (918) 631-2204. Fax: (918) 631-2762. E-mail: brad-amendt{at}utulsa.edu.

Molecular and Cellular Biology, October 1999, p. 7001-7010, Vol. 19, No. 10
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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