Logo image
Multifunctional Role of the Pitx2 Homeodomain Protein C-Terminal Tail
Journal article   Peer reviewed

Multifunctional Role of the Pitx2 Homeodomain Protein C-Terminal Tail

Brad A Amendt, Lillian B Sutherland and Andrew F Russo
Molecular and cellular biology, Vol.19(10), pp.7001-7010
10/1999
DOI: 10.1128/MCB.19.10.7001
PMCID: PMC84695
PMID: 10490637

View Online

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.
Transcriptional Regulation

Details

Metrics

Logo image