Brn-3a/POU4F1 interacts with and differentially affects p73-mediated transcription.

Cell Death and Differentiation
Chantelle D HudsonVishwanie S Budhram-Mahadeo

Abstract

The Brn-3a/POU4F1 POU transcription factor is critical for the survival and differentiation of specific sensory neurons during development or upon injury; by regulating expression of target genes, either directly or indirectly upon interaction with other proteins. In this study, we demonstrated the physical interaction of Brn-3a with different p73 isoforms and showed co-localization in sensory neurons arising from the neural crest. The biological effects of p73/ Brn-3a interaction depend on the particular p73 isoform, because co-expression of Brn-3a with TAp73 enhanced cell cycle arrest, whereas Brn-3a and DeltaNp73 cooperated to increase protection from apoptosis. Brn-3a antagonized TAp73 transactivation of pro-apoptotic Bax, but co-operated to increase transcription of the cell cycle regulator p21 CIP1/Waf1. The region 425-494 amino acids within the TAp73 C terminus were critical for Brn-3a to repress Bax transactivation, but not for cooperation on the p21 CIP1/Waf1 promoter. Our results suggest that co-factors binding to the p73 C terminus facilitate maximal activation on the Bax but not p21 CIP1/Waf1 promoter and that Brn-3a modulates this interaction. Thus, the physical interaction of Brn-3a with specific p73 isoforms will...Continue Reading

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Citations

Sep 20, 2011·Journal of Cancer Research and Clinical Oncology·Biswa Pratim Das Purkayastha, Jagat Kumar Roy
Mar 17, 2010·The Journal of Biological Chemistry·Daniel C BerwickDavid S Latchman
Oct 30, 2020·Frontiers in Integrative Neuroscience·Jie ChenLinqing Miao

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