Over-expression of cyclin D1 regulates Cdk4 protein synthesis

M. A. Parker, N. G. Deane, E Aubrey Thompson, R. H. Whitehead, S. K. Mithani, M. K. Washington, P. K. Datta, D. A. Dixon, R. D. Beauchamp

Research output: Contribution to journalArticle

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Abstract

Increased Cdk4 expression occurs coincident with over-expression of cyclin D1 in many human tumours and tumourigenic mouse models. Here, we investigate both in vivo and in vitro the mechanism by which Cdk4 expression is regulated in the context of cyclin D1 over-expression. Cdk4 mRNA levels in cyclin D1-over-expressing tissue and cultured cells were unchanged compared with controls. In contrast, Cdk4 protein levels were increased in cyclin D1-over-expressing tissue and cells versus their respective controls. This increase was not due to altered protein stability, but appeared to be due to an increase in Cdk4 protein synthesis. We also performed immunoprecipitation and in vitro kinase assays to demonstrate an increase in cyclin D1-Cdk4 complex formation and associated kinase activity. Blocking cyclin D1 expression resulted in diminished Cdk4 protein but not mRNA levels. These findings suggest a mechanism by which Cdk4 expression is increased in the context of cyclin D1 over-expression during tumourigenesis.

Original languageEnglish (US)
Pages (from-to)347-360
Number of pages14
JournalCell Proliferation
Volume36
Issue number6
DOIs
StatePublished - Dec 2003
Externally publishedYes

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Cyclin-Dependent Kinase 4
Cyclin D1
Phosphotransferases
Messenger RNA
Protein Stability
Immunoprecipitation
Cultured Cells

ASJC Scopus subject areas

  • Cell Biology

Cite this

Parker, M. A., Deane, N. G., Thompson, E. A., Whitehead, R. H., Mithani, S. K., Washington, M. K., ... Beauchamp, R. D. (2003). Over-expression of cyclin D1 regulates Cdk4 protein synthesis. Cell Proliferation, 36(6), 347-360. https://doi.org/10.1046/j.1365-2184.2003.00290.x

Over-expression of cyclin D1 regulates Cdk4 protein synthesis. / Parker, M. A.; Deane, N. G.; Thompson, E Aubrey; Whitehead, R. H.; Mithani, S. K.; Washington, M. K.; Datta, P. K.; Dixon, D. A.; Beauchamp, R. D.

In: Cell Proliferation, Vol. 36, No. 6, 12.2003, p. 347-360.

Research output: Contribution to journalArticle

Parker, MA, Deane, NG, Thompson, EA, Whitehead, RH, Mithani, SK, Washington, MK, Datta, PK, Dixon, DA & Beauchamp, RD 2003, 'Over-expression of cyclin D1 regulates Cdk4 protein synthesis', Cell Proliferation, vol. 36, no. 6, pp. 347-360. https://doi.org/10.1046/j.1365-2184.2003.00290.x
Parker MA, Deane NG, Thompson EA, Whitehead RH, Mithani SK, Washington MK et al. Over-expression of cyclin D1 regulates Cdk4 protein synthesis. Cell Proliferation. 2003 Dec;36(6):347-360. https://doi.org/10.1046/j.1365-2184.2003.00290.x
Parker, M. A. ; Deane, N. G. ; Thompson, E Aubrey ; Whitehead, R. H. ; Mithani, S. K. ; Washington, M. K. ; Datta, P. K. ; Dixon, D. A. ; Beauchamp, R. D. / Over-expression of cyclin D1 regulates Cdk4 protein synthesis. In: Cell Proliferation. 2003 ; Vol. 36, No. 6. pp. 347-360.
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