In:
Biochemical Journal, Portland Press Ltd., Vol. 417, No. 1 ( 2009-01-01), p. 235-246
Abstract:
The heterodimeric HIF (hypoxia-inducible factor)-1 is a transcriptional master regulator of several genes involved in mammalian oxygen homoeostasis. Besides the well described regulation of the HIF-1α subunit via hydroxylation-mediated protein stability in hypoxia, there are several indications of an additional translational control of the HIF-1α mRNA, especially after growth factor stimulation. We identified an interaction of CPEB (cytoplasmic polyadenylation-element-binding protein) 1 and CPEB2 with the 3′-UTR (untranslated region) of HIF-1α mRNA. Overexpression of CPEB1 and CPEB2 affected HIF-1α protein levels mediated by the 3′-UTR of HIF-1α mRNA. Stimulation of neuroblastoma SK-N-MC cells with insulin and thus activation of endogenous CPEBs increased the expression of a luciferase reporter gene fused to the 3′-UTR of HIF-1α as well as endogenous HIF-1α protein levels. This could be abrogated by treating the cells with CPEB1 or CPEB2 siRNAs (short interfering RNAs). Injection of HIF-1α cRNA into Xenopus oocytes verified the elongation of the poly(A)+ (polyadenylated) tail by cytoplasmic polyadenylation. Thus CPEB1 and CPEB2 are involved in the regulation of HIF-1α following insulin stimulation.
Type of Medium:
Online Resource
ISSN:
0264-6021
,
1470-8728
Language:
English
Publisher:
Portland Press Ltd.
Publication Date:
2009
detail.hit.zdb_id:
1473095-9
SSG:
12
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