Tumor suppressor protein VHL inhibits Hedgehog-Gli activation through suppression of Gli1 nuclear localization

► Tumor suppressor protein VHL decreases the expression of Hedgehog-Gli1 gene. ► VHL represses Gli1-mediated Hedgehog target gene expression. ► VHL interacts directly with Gli1 protein. ► VHL co-localizes with Gli1 in the cytoplasm and disturbs Gli1 nuclear localization. ► These results suggest that VHL may act as a tumor suppressor in some Hedgehog-related cancers.