Control of Cyclin-Dependent Kinase Inhibitor p27 Expression by Cap-Independent Translation
AUTOR(ES)
Miskimins, W. Keith
FONTE
American Society for Microbiology
RESUMO
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.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=87223Documentos Relacionados
- Inactivation of the cyclin-dependent kinase inhibitor p27 upon loss of the tuberous sclerosis complex gene-2
- Modulation of apoptosis by the cyclin-dependent kinase inhibitor p27Kip1
- Cloning and characterization of the Xenopus cyclin-dependent kinase inhibitor p27XIC1.
- Growth arrest by the cyclin-dependent kinase inhibitor p27Kip1 is abrogated by c-Myc.
- The cyclin-dependent kinase inhibitor p27Kip1 induces N-terminal proteolytic cleavage of cyclin A