TSGA10 prevents nuclear localization of the hypoxia-inducible factor (HIF)-1alpha.

The hypoxia-inducible factor (HIF)-1 is a transcriptional regulator of genes involved in oxygen homeostasis. We previously described testis-specific isoforms of HIF-1alpha (mHIF-1alphaI.1 and hHIF-1alphaTe). Using mHIF-1alpha exon I.1 knock-out mice we confirmed the specific expression of mHIF-1alphaI.1 in the sperm tail. A protein-protein interaction between HIF-1alpha and the testis specific gene antigen 10 (TSGA10) was identified by yeast two-hybrid screening. TSGA10 is expressed in testis but also in other organs and malignant tissues. Immunofluorescence analysis indicated that the C-terminal part of TSGA10 accumulates in the midpiece of spermatozoa, where it co-localizes with HIF-1alpha. HIF-1alpha nuclear localization and HIF-1 transcriptional activity were significantly affected by overexpressed TSGA10.