The heterodimeric hypoxia-inducible factor (HIF)-1 is a transcriptional master regulator of several genes involved in mammalian oxygen homeostasis. Besides the well described regulation of the a-subunit via hydroxylation-mediated protein stability, there are some indications for an additional translational control. In this regard, we identified a protein interaction of mouse and human HIF-1a with the cytoplasmic polyadenylation element binding protein (CPEB2). Further studies demonstrated that CPEB 1 and 2 also bind to a putative CPE in the 3'UTR of HIF-1a. Overexpression of CPEB1 and 2 resulted in downregulation of HIF-1a protein expression without changes in RNA expression in hypoxia (1% O2 for 4 hours). In addition, CPEB1 and 2 affected the expression of a reportergene, which was fused to the 3'UTR of HIF-1a, whereas the 5'UTR of HIF-1a did not show any effect. CPEB1 and 2 RNA expression did show a selective organ distribution with high levels in the brain, skeletal muscle and testis. Exposing the neuronal SK-N-MC or H4 cells to hypoxia (1% O2 for 4 hours) or exposure of mice to inspiratory 7.5% O2 did not change the expression of CPEB1 and 2.