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Dephosphorylation of p53 at Ser20 after cellular exposure to low levels of non-ionizing radiation

Dephosphorylation of p53 at Ser20 after cellular exposure to low levels of non-ionizing radiation
Dephosphorylation of p53 at Ser20 after cellular exposure to low levels of non-ionizing radiation
Induction of the transactivation function of p53 after cellular irradiation was studied under conditions in which upstream signaling events modulating p53 activation were uncoupled from those regulating stabilization. This investigation prompted the discovery of a novel radiation-responsive kinase pathway targeting Ser20 that results in the masking of the DO-1 epitope in undamaged cells. Unmasking of the DO-1 epitope via dephosphorylation occurs in response to low doses of non-ionizing radiation. Our data show that phosphorylation at Ser20 reduces binding of the mdm2 protein, suggesting that a function of the Ser20-kinase pathway may be to produce a stable pool of inactive p53 in undamaged cells which can be readily activated after cellular injury. Phospho-specific monoclonal antibodies were used to determine whether the Ser20 signaling pathway is coupled to the Ser15 and Ser392 radiation-responsive kinase pathways. These results demonstrated that: (1) dephosphorylation at Ser20 is co-ordinated with an increased steady-state phosphorylation at Ser392 after irradiation, without p53 protein stabilization, and (2) stabilization of p53 protein can occur without Ser15 phosphorylation at higher doses of radiation. These data show that the Ser20 and Ser392 phosphorylation sites are both targeted by an integrated network of signaling pathways which is acutely sensitive to radiation injury.
0950-9232
6305-6312
Craig, A.L.
05e9b28c-0f2c-48c9-9d3e-b6cd13a6eb30
Blaydes, J. P.
e957f999-fd91-4f77-ad62-5b4ef069b15b
Burch, L.R.
f6ecae08-9646-49a3-b829-9ac529d05fa2
Thompson, A.M.
117ac14a-d57c-4cc5-a3b2-cd3dd90a156f
Hupp, T.R.
da952289-a4c5-4280-8f9f-e4a28cc141a5
Craig, A.L.
05e9b28c-0f2c-48c9-9d3e-b6cd13a6eb30
Blaydes, J. P.
e957f999-fd91-4f77-ad62-5b4ef069b15b
Burch, L.R.
f6ecae08-9646-49a3-b829-9ac529d05fa2
Thompson, A.M.
117ac14a-d57c-4cc5-a3b2-cd3dd90a156f
Hupp, T.R.
da952289-a4c5-4280-8f9f-e4a28cc141a5

Craig, A.L., Blaydes, J. P., Burch, L.R., Thompson, A.M. and Hupp, T.R. (1999) Dephosphorylation of p53 at Ser20 after cellular exposure to low levels of non-ionizing radiation. Oncogene, 18 (46), 6305-6312.

Record type: Article

Abstract

Induction of the transactivation function of p53 after cellular irradiation was studied under conditions in which upstream signaling events modulating p53 activation were uncoupled from those regulating stabilization. This investigation prompted the discovery of a novel radiation-responsive kinase pathway targeting Ser20 that results in the masking of the DO-1 epitope in undamaged cells. Unmasking of the DO-1 epitope via dephosphorylation occurs in response to low doses of non-ionizing radiation. Our data show that phosphorylation at Ser20 reduces binding of the mdm2 protein, suggesting that a function of the Ser20-kinase pathway may be to produce a stable pool of inactive p53 in undamaged cells which can be readily activated after cellular injury. Phospho-specific monoclonal antibodies were used to determine whether the Ser20 signaling pathway is coupled to the Ser15 and Ser392 radiation-responsive kinase pathways. These results demonstrated that: (1) dephosphorylation at Ser20 is co-ordinated with an increased steady-state phosphorylation at Ser392 after irradiation, without p53 protein stabilization, and (2) stabilization of p53 protein can occur without Ser15 phosphorylation at higher doses of radiation. These data show that the Ser20 and Ser392 phosphorylation sites are both targeted by an integrated network of signaling pathways which is acutely sensitive to radiation injury.

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Published date: 4 November 1999

Identifiers

Local EPrints ID: 150565
URI: http://eprints.soton.ac.uk/id/eprint/150565
ISSN: 0950-9232
PURE UUID: 494a2294-aa73-40af-9952-adc090be8844
ORCID for J. P. Blaydes: ORCID iD orcid.org/0000-0001-8525-0209

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Date deposited: 20 Jul 2010 13:41
Last modified: 16 Sep 2020 01:34

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Contributors

Author: A.L. Craig
Author: J. P. Blaydes ORCID iD
Author: L.R. Burch
Author: A.M. Thompson
Author: T.R. Hupp

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