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

Brn-3a/POU4F1 interacts with and differentially affects p73-mediated transcription
Brn-3a/POU4F1 interacts with and differentially affects p73-mediated transcription
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 ?Np73 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 p21CIP1/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 p21CIP1/Waf1 promoter. Our results suggest that co-factors binding to the p73 C terminus facilitate maximal activation on the Bax but not p21CIP1/Waf1 promoter and that Brn-3a modulates this interaction. Thus, the physical interaction of Brn-3a with specific p73 isoforms will be critical for determining cell fate during neuronal development or in injured neurons expressing both factors.

1350-9047
1266-1278
Hudson, C.D.
f6ddb4e7-605e-4c01-882b-3ca3cc2a7a06
Sayan, A.E.
d1dbbcad-9c53-47c1-8b7e-1b45cc56e077
Melino, G.
8704cb29-7407-416a-be51-a7efd06144c9
Knight, R.A.
a48d0c42-7876-4bf9-808b-cfe88d5dfb3c
Latchman, D.S.
d694ae39-32ec-4da7-b024-aebd3ceb6687
Budhram-Mahadeo, V.
180706bf-8a19-4a85-aa83-3899e1caf2a4
Hudson, C.D.
f6ddb4e7-605e-4c01-882b-3ca3cc2a7a06
Sayan, A.E.
d1dbbcad-9c53-47c1-8b7e-1b45cc56e077
Melino, G.
8704cb29-7407-416a-be51-a7efd06144c9
Knight, R.A.
a48d0c42-7876-4bf9-808b-cfe88d5dfb3c
Latchman, D.S.
d694ae39-32ec-4da7-b024-aebd3ceb6687
Budhram-Mahadeo, V.
180706bf-8a19-4a85-aa83-3899e1caf2a4

Hudson, C.D., Sayan, A.E., Melino, G., Knight, R.A., Latchman, D.S. and Budhram-Mahadeo, V. (2008) Brn-3a/POU4F1 interacts with and differentially affects p73-mediated transcription. Cell Death and Differentiation, 15 (8), 1266-1278. (doi:10.1038/cdd.2008.45).

Record type: Article

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 ?Np73 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 p21CIP1/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 p21CIP1/Waf1 promoter. Our results suggest that co-factors binding to the p73 C terminus facilitate maximal activation on the Bax but not p21CIP1/Waf1 promoter and that Brn-3a modulates this interaction. Thus, the physical interaction of Brn-3a with specific p73 isoforms will be critical for determining cell fate during neuronal development or in injured neurons expressing both factors.

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Published date: April 2008
Organisations: Cancer Sciences

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Local EPrints ID: 341628
URI: https://eprints.soton.ac.uk/id/eprint/341628
ISSN: 1350-9047
PURE UUID: 226bf4b4-efbb-47c1-a94f-80bffc072b68

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Date deposited: 31 Jul 2012 16:16
Last modified: 18 Jul 2017 05:33

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Contributors

Author: C.D. Hudson
Author: A.E. Sayan
Author: G. Melino
Author: R.A. Knight
Author: D.S. Latchman
Author: V. Budhram-Mahadeo

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