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Vol. 16, No. 23, pp. 3087-3099, December 1, 2002
Max-Planck-Institute of Biochemistry, Am Klopferspitz 18a, D-82152
Martinsried, Germany
p27Kip1 restrains cell proliferation by binding to
and inhibiting cyclin-dependent kinases. To investigate the mechanisms
of p27 translational regulation, we isolated a complete p27 cDNA and identified an internal ribosomal entry site (IRES) located in its
5'UTR. The IRES allows for efficient p27 translation under conditions
where cap-dependent translation is reduced. Searching for possible
regulators of IRES activity we have identified the neuronal ELAV
protein HuD as a specific binding factor of the p27 5'UTR. Increased
expression of HuD or the ubiquitously expressed HuR protein
specifically inhibits p27 translation and p27 IRES activity. Consistent
with an inhibitory role of Hu proteins in p27 translation, siRNA
mediated knockdown of HuR induced endogenous p27 protein levels as well
as IRES-mediated reporter translation and leads to cell cycle arrest in
G1.
[Key Words: Cell division cycle; translation; p27 Kip1; IRES; HuD; HuR; ELAV]
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