Control of cyclin-dependent kinase inhibitor p27 expression by cap-independent translation

W. K. Miskimins, G. Wang, M. Hawkinson, Robin Miskimins

Research output: Contribution to journalArticle

80 Citations (Scopus)

Abstract

p27 is a key regulator of cell proliferation through inhibition of G1 cyclin-dependent kinase (CDK) activity. Translation of the p27 mRNA is an important control mechanism for determining cellular levels of the inhibitor. Nearly all eukaryotic mRNAs are translated through a mechanism involving recognition of the 5′ cap by eukaryotic initiation factor 4E (eIF4E). In quiescent cells eIF4E activity is repressed, leading to a global decline in translation rates. In contrast, p27 translation is highest during quiescence, suggesting that it escapes the general repression of translational initiation. We show that the 5′ untranslated region (5′-UTR) of the p27 mRNA mediates cap-independent translation. This activity is unaffected by conditions in which eIF4E is inhibited. In D6P2T cells, elevated cyclic AMP levels cause a rapid withdrawal from the cell cycle that is correlated with a striking increase in p27. Under these same conditions, cap-independent translation from the p27 5′-UTR is enhanced. These results indicate that regulation of internal initiation of translation is an important determinant of p27 protein levels.

Original languageEnglish (US)
Pages (from-to)4960-4967
Number of pages8
JournalMolecular and cellular biology
Volume21
Issue number15
DOIs
StatePublished - Jul 28 2001

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Eukaryotic Initiation Factor-4E
Cyclin-Dependent Kinase Inhibitor p27
5' Untranslated Regions
Messenger RNA
Cyclin-Dependent Kinases
Protein Biosynthesis
Cyclic AMP
Cell Cycle
Cell Proliferation
Proteins

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Control of cyclin-dependent kinase inhibitor p27 expression by cap-independent translation. / Miskimins, W. K.; Wang, G.; Hawkinson, M.; Miskimins, Robin.

In: Molecular and cellular biology, Vol. 21, No. 15, 28.07.2001, p. 4960-4967.

Research output: Contribution to journalArticle

Miskimins, W. K. ; Wang, G. ; Hawkinson, M. ; Miskimins, Robin. / Control of cyclin-dependent kinase inhibitor p27 expression by cap-independent translation. In: Molecular and cellular biology. 2001 ; Vol. 21, No. 15. pp. 4960-4967.
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