The mechanisms of regulation of Hdm2 protein level by serum growth factors
The mechanisms of regulation of Hdm2 protein level by serum growth factors
Cell cycle progression in response to serum growth factors is dependent on the expression of functional Hdm2 (Mdm2), which inhibits p53-dependent transcription of anti-proliferative genes. In a well characterised non-transformed human fibroblast model, growth factors induce the expression of Hdm2 with rapid kinetics. Here we dissect the mechanistic basis for this critical response. In contrast to previous studies in which components of the growth factor signalling pathways were overexpressed, hdm2 mRNA expression is not induced with immediate-early kinetics in these cells. Rather, the elevated Hdm2 protein levels which follow growth factor stimulation are primarily a consequence of phosphatidylinositol-3 kinase-dependent stabilisation of the Hdm2 protein combined with a global increase in protein synthesis.
p53, mdm2, mitogen-activated protein kinase, v-akt murine thymoma viral oncogene homologue kinase, growth factor
300-304
Phillips, Anna
ff19f307-7df7-43a4-84a9-5e015c448356
Jones, Chris J.
9bfd230c-4cd3-4ad9-8d09-f10b0113e920
Blaydes, Jeremy P.
e957f999-fd91-4f77-ad62-5b4ef069b15b
9 January 2006
Phillips, Anna
ff19f307-7df7-43a4-84a9-5e015c448356
Jones, Chris J.
9bfd230c-4cd3-4ad9-8d09-f10b0113e920
Blaydes, Jeremy P.
e957f999-fd91-4f77-ad62-5b4ef069b15b
Phillips, Anna, Jones, Chris J. and Blaydes, Jeremy P.
(2006)
The mechanisms of regulation of Hdm2 protein level by serum growth factors.
FEBS Letters, 580 (1), .
(doi:10.1016/j.febslet.2005.12.026).
Abstract
Cell cycle progression in response to serum growth factors is dependent on the expression of functional Hdm2 (Mdm2), which inhibits p53-dependent transcription of anti-proliferative genes. In a well characterised non-transformed human fibroblast model, growth factors induce the expression of Hdm2 with rapid kinetics. Here we dissect the mechanistic basis for this critical response. In contrast to previous studies in which components of the growth factor signalling pathways were overexpressed, hdm2 mRNA expression is not induced with immediate-early kinetics in these cells. Rather, the elevated Hdm2 protein levels which follow growth factor stimulation are primarily a consequence of phosphatidylinositol-3 kinase-dependent stabilisation of the Hdm2 protein combined with a global increase in protein synthesis.
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MDM2-fibroblast_v2.pdf
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Published date: 9 January 2006
Keywords:
p53, mdm2, mitogen-activated protein kinase, v-akt murine thymoma viral oncogene homologue kinase, growth factor
Identifiers
Local EPrints ID: 26524
URI: http://eprints.soton.ac.uk/id/eprint/26524
ISSN: 0014-5793
PURE UUID: 27092a4e-7f5c-47ae-967b-46280d3587ac
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Date deposited: 19 Apr 2006
Last modified: 16 Mar 2024 03:18
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Author:
Anna Phillips
Author:
Chris J. Jones
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