Regulation of BAG-1 IRES-mediated translation following chemotoxic stress
Regulation of BAG-1 IRES-mediated translation following chemotoxic stress
There are three major isoforms of BAG-1 in mammalian cells, termed BAG-1L (p50), BAG-1M (p46) and BAG-1S (p36) that function as pro-survival proteins and are associated with tumorigenesis and chemoresistance. Initiation of BAG-1 protein synthesis can occur by both cap-dependent and cap-independent mechanisms and it has been shown that synthesis of BAG-1S is dependent upon the presence of an internal ribosome entry segment (IRES) in the 5'-UTR of BAG-1 mRNA. We have shown previously that BAG-1 IRES-meditated initiation of translation requires two trans-acting factors poly (rC) binding protein 1 (PCBP1) and polypyrimidine tract binding protein (PTB) for function. The former protein allows BAG-1 IRES RNA to attain a structure that permits binding of the ribosome, while the latter protein appears to be involved in ribosome recruitment. Here, we show that the BAG-1 IRES maintains synthesis of BAG-1 protein following exposure of cells to the chemotoxic drug vincristine but not to cisplatin and that this is brought about, in part, by the relocalization of PTB and PCBP1 from the nucleus to the cytoplasm.
1167-1174
Dobbyn, H.C.
32e539a7-a217-4530-a26b-d4473a1170ff
Hill, K.
bd570b53-57c8-4a24-aad7-c5012db565e1
Hamilton, T.L.
df35078f-2065-43c5-a8b7-925139383f6f
Spriggs, K.A.
39838c5d-1013-4db3-9173-60d2eb1ac9a4
Pickering, B.M.
33fb6c48-ca72-4e0f-9a54-9cab462c1c16
Coldwell, M.J.
a3432799-ed45-4948-9f7a-2a284d3ec65c
de Moor, C.H.
4054b50f-eb2f-48bb-9009-ea4c5df00981
Bushell, M.
a0f7666f-d5b5-4c2e-a308-cbf368b5d931
Willis, A.E.
8be1c6a2-d88e-4ced-bcca-7b54fa96a694
14 February 2008
Dobbyn, H.C.
32e539a7-a217-4530-a26b-d4473a1170ff
Hill, K.
bd570b53-57c8-4a24-aad7-c5012db565e1
Hamilton, T.L.
df35078f-2065-43c5-a8b7-925139383f6f
Spriggs, K.A.
39838c5d-1013-4db3-9173-60d2eb1ac9a4
Pickering, B.M.
33fb6c48-ca72-4e0f-9a54-9cab462c1c16
Coldwell, M.J.
a3432799-ed45-4948-9f7a-2a284d3ec65c
de Moor, C.H.
4054b50f-eb2f-48bb-9009-ea4c5df00981
Bushell, M.
a0f7666f-d5b5-4c2e-a308-cbf368b5d931
Willis, A.E.
8be1c6a2-d88e-4ced-bcca-7b54fa96a694
Dobbyn, H.C., Hill, K., Hamilton, T.L., Spriggs, K.A., Pickering, B.M., Coldwell, M.J., de Moor, C.H., Bushell, M. and Willis, A.E.
(2008)
Regulation of BAG-1 IRES-mediated translation following chemotoxic stress.
Oncogene, 27 (8), .
(doi:10.1038/sj.onc.1210723).
(PMID:17700523)
Abstract
There are three major isoforms of BAG-1 in mammalian cells, termed BAG-1L (p50), BAG-1M (p46) and BAG-1S (p36) that function as pro-survival proteins and are associated with tumorigenesis and chemoresistance. Initiation of BAG-1 protein synthesis can occur by both cap-dependent and cap-independent mechanisms and it has been shown that synthesis of BAG-1S is dependent upon the presence of an internal ribosome entry segment (IRES) in the 5'-UTR of BAG-1 mRNA. We have shown previously that BAG-1 IRES-meditated initiation of translation requires two trans-acting factors poly (rC) binding protein 1 (PCBP1) and polypyrimidine tract binding protein (PTB) for function. The former protein allows BAG-1 IRES RNA to attain a structure that permits binding of the ribosome, while the latter protein appears to be involved in ribosome recruitment. Here, we show that the BAG-1 IRES maintains synthesis of BAG-1 protein following exposure of cells to the chemotoxic drug vincristine but not to cisplatin and that this is brought about, in part, by the relocalization of PTB and PCBP1 from the nucleus to the cytoplasm.
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e-pub ahead of print date: 13 August 2007
Published date: 14 February 2008
Organisations:
Biological Sciences
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Local EPrints ID: 142023
URI: http://eprints.soton.ac.uk/id/eprint/142023
ISSN: 0950-9232
PURE UUID: 9741759c-7a49-4bd7-a801-6ea6698b1e1e
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Date deposited: 01 Apr 2010 15:28
Last modified: 14 Mar 2024 00:38
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Author:
H.C. Dobbyn
Author:
K. Hill
Author:
T.L. Hamilton
Author:
K.A. Spriggs
Author:
B.M. Pickering
Author:
M.J. Coldwell
Author:
C.H. de Moor
Author:
M. Bushell
Author:
A.E. Willis
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