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The BAG-1 cochaperone is a negative regulator of p73-dependent transcription.

The BAG-1 cochaperone is a negative regulator of p73-dependent transcription.
The BAG-1 cochaperone is a negative regulator of p73-dependent transcription.
High-level expression of Bcl-2 associated athanogene (BAG-1) protects cancer cells from stress-induced cell death and growth inhibition. These protective effects of BAG-1 are dependent on interactions with the HSC70 and HSP70 chaperones. However, the key stress-response molecules that are regulated by a BAG-1/chaperone mechanism have not been identified. In this study, we investigated the effects of BAG-1 overexpression on the function of p53 family proteins, p53, p63 and p73. Overexpression of BAG-1 isoforms interfered with the transactivating activity of p73 and p63, but had modest and variable effects on p53-dependent transcription. p73 and BAG-1 interacted in intact cells and overexpression of BAG-1 decreased the expression of p73. siRNA-mediated ablation of endogenous BAG-1 increased the activity of a p73-responsive promoter and this was reversed by knock-down of p73. The ability of BAG-1 to modulate p73 activity and expression, and to interact with p73 were dependent on amino acid residues required for the interaction of BAG-1 with HSC70 and HSP70. These results show that BAG-1 inhibits the transactivating functions of p73 and provide new insight into the mechanisms that control the expression of p73. Inhibition of p73 function may be one mechanism that contributes to the pro-survival activity of BAG-1
0007-0920
1347-1357
Wang, X.-H.
4f406ce1-a2f7-4b85-8475-1d3c356d98ca
O'Connor, D.
c4910888-1df5-4be7-8142-af0e919f9100
Brimmell, M.
4bb675a5-c3f0-4ddb-ae49-d39257ba79e1
Packham, G.
fdabe56f-2c58-469c-aadf-38878f233394
Wang, X.-H.
4f406ce1-a2f7-4b85-8475-1d3c356d98ca
O'Connor, D.
c4910888-1df5-4be7-8142-af0e919f9100
Brimmell, M.
4bb675a5-c3f0-4ddb-ae49-d39257ba79e1
Packham, G.
fdabe56f-2c58-469c-aadf-38878f233394

Wang, X.-H., O'Connor, D., Brimmell, M. and Packham, G. (2009) The BAG-1 cochaperone is a negative regulator of p73-dependent transcription. British Journal of Cancer, 100, 1347-1357. (doi:10.1038/sj.bjc.6604985).

Record type: Article

Abstract

High-level expression of Bcl-2 associated athanogene (BAG-1) protects cancer cells from stress-induced cell death and growth inhibition. These protective effects of BAG-1 are dependent on interactions with the HSC70 and HSP70 chaperones. However, the key stress-response molecules that are regulated by a BAG-1/chaperone mechanism have not been identified. In this study, we investigated the effects of BAG-1 overexpression on the function of p53 family proteins, p53, p63 and p73. Overexpression of BAG-1 isoforms interfered with the transactivating activity of p73 and p63, but had modest and variable effects on p53-dependent transcription. p73 and BAG-1 interacted in intact cells and overexpression of BAG-1 decreased the expression of p73. siRNA-mediated ablation of endogenous BAG-1 increased the activity of a p73-responsive promoter and this was reversed by knock-down of p73. The ability of BAG-1 to modulate p73 activity and expression, and to interact with p73 were dependent on amino acid residues required for the interaction of BAG-1 with HSC70 and HSP70. These results show that BAG-1 inhibits the transactivating functions of p73 and provide new insight into the mechanisms that control the expression of p73. Inhibition of p73 function may be one mechanism that contributes to the pro-survival activity of BAG-1

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Published date: 2009

Identifiers

Local EPrints ID: 73182
URI: http://eprints.soton.ac.uk/id/eprint/73182
ISSN: 0007-0920
PURE UUID: de2ffc80-4bf6-487f-8893-fa3cba387c1c
ORCID for G. Packham: ORCID iD orcid.org/0000-0002-9232-5691

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Date deposited: 03 Mar 2010
Last modified: 14 Mar 2024 02:44

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Contributors

Author: X.-H. Wang
Author: D. O'Connor
Author: M. Brimmell
Author: G. Packham ORCID iD

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