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The retinoblastoma protein interacts with Bag-1 in human colonic adenoma and carcinoma derived cell lines

The retinoblastoma protein interacts with Bag-1 in human colonic adenoma and carcinoma derived cell lines
The retinoblastoma protein interacts with Bag-1 in human colonic adenoma and carcinoma derived cell lines
Although the retinoblastoma susceptibility gene RB1 is inactivated in a wide range of human tumours, overexpression in colonic carcinomas has been linked to the antiapoptotic function of the protein. In the current study we show that the Retinoblastoma susceptibility protein (Rb) protein interacts with Bag-1, an apoptotic regulator, in human colonic adenoma- and carcinoma-derived cell lines. Coimmunoprecipitation demonstrated that endogenous Rb and Bag-1 interact in both adenoma- and carcinoma-derived cell lines. The specificity of the interaction was demonstrated by expression of human Papillomavirus E7 oncoprotein, an inhibitor of Rb protein interactions, which disrupted the Rb/Bag-1 complex. We report that Bag-1 is predominantly localised in the nucleus of colorectal adenoma- and carcinoma-derived epithelial cells. Disruption of the Rb/Bag-1 complex through expression of E7 changes the subcellular distribution of Bag-1, decreasing nuclear localised Bag-1. Our work establishes that the Rb protein interacts with the Bag-1 apoptotic regulator protein, and introduces a novel function for Rb, involving modulation of the subcellular localisation of Bag-1 in human colonic epithelial cells.
retinoblastoma, bag-1, human, colon, interaction
0020-7136
364-371
Arhel, Nathalie J.
e2a4c609-8591-4b1b-9c85-7fff09f23cbd
Packham, Graham
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Townsend, Paul A.
a2680443-664e-46d0-b4dd-97456ba810db
Collard, Tracey J.
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H-Zadeh, Akram M.
cc95f449-2841-4911-ac22-61ed2361489e
Sharp, Adam
f26a1894-b10f-4864-a314-750628d6c0cc
Cutress, Ramsey I.
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Malik, Karim
aea86ec1-75a7-4271-829e-9d1570ee0c0f
Hague, Angela
0e1199e4-08c3-4e8b-b40f-2fc61555e6f4
Paraskeva, Chris
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Williams, Ann C.
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Arhel, Nathalie J.
e2a4c609-8591-4b1b-9c85-7fff09f23cbd
Packham, Graham
fdabe56f-2c58-469c-aadf-38878f233394
Townsend, Paul A.
a2680443-664e-46d0-b4dd-97456ba810db
Collard, Tracey J.
fa7fb6aa-efbe-4dc2-b978-92dbd8c96025
H-Zadeh, Akram M.
cc95f449-2841-4911-ac22-61ed2361489e
Sharp, Adam
f26a1894-b10f-4864-a314-750628d6c0cc
Cutress, Ramsey I.
68ae4f86-e8cf-411f-a335-cdba51797406
Malik, Karim
aea86ec1-75a7-4271-829e-9d1570ee0c0f
Hague, Angela
0e1199e4-08c3-4e8b-b40f-2fc61555e6f4
Paraskeva, Chris
fbcbc612-207a-42a8-b54a-463180ea1768
Williams, Ann C.
754a6874-3c07-4c28-b7c5-d3bafab6fdb5

Arhel, Nathalie J., Packham, Graham, Townsend, Paul A., Collard, Tracey J., H-Zadeh, Akram M., Sharp, Adam, Cutress, Ramsey I., Malik, Karim, Hague, Angela, Paraskeva, Chris and Williams, Ann C. (2003) The retinoblastoma protein interacts with Bag-1 in human colonic adenoma and carcinoma derived cell lines. International Journal of Cancer, 106 (3), 364-371. (doi:10.1002/ijc.11257). (PMID:12845674)

Record type: Article

Abstract

Although the retinoblastoma susceptibility gene RB1 is inactivated in a wide range of human tumours, overexpression in colonic carcinomas has been linked to the antiapoptotic function of the protein. In the current study we show that the Retinoblastoma susceptibility protein (Rb) protein interacts with Bag-1, an apoptotic regulator, in human colonic adenoma- and carcinoma-derived cell lines. Coimmunoprecipitation demonstrated that endogenous Rb and Bag-1 interact in both adenoma- and carcinoma-derived cell lines. The specificity of the interaction was demonstrated by expression of human Papillomavirus E7 oncoprotein, an inhibitor of Rb protein interactions, which disrupted the Rb/Bag-1 complex. We report that Bag-1 is predominantly localised in the nucleus of colorectal adenoma- and carcinoma-derived epithelial cells. Disruption of the Rb/Bag-1 complex through expression of E7 changes the subcellular distribution of Bag-1, decreasing nuclear localised Bag-1. Our work establishes that the Rb protein interacts with the Bag-1 apoptotic regulator protein, and introduces a novel function for Rb, involving modulation of the subcellular localisation of Bag-1 in human colonic epithelial cells.

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More information

Published date: 2003
Keywords: retinoblastoma, bag-1, human, colon, interaction

Identifiers

Local EPrints ID: 24613
URI: http://eprints.soton.ac.uk/id/eprint/24613
ISSN: 0020-7136
PURE UUID: 4b951769-71d4-433d-887d-dd4e055369f1
ORCID for Graham Packham: ORCID iD orcid.org/0000-0002-9232-5691

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Date deposited: 03 Apr 2006
Last modified: 23 Jul 2022 01:46

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Contributors

Author: Nathalie J. Arhel
Author: Graham Packham ORCID iD
Author: Paul A. Townsend
Author: Tracey J. Collard
Author: Akram M. H-Zadeh
Author: Adam Sharp
Author: Karim Malik
Author: Angela Hague
Author: Chris Paraskeva
Author: Ann C. Williams

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