title: Tumor suppressor protein VHL inhibits Hedgehog-Gli activation through suppression of Gli1 nuclear localization.
abstract: The transcription factor Gli1 acts in the last known step of the Hedgehog signaling, and deregulation of Gli1 is implicated in human cancers. VHL protein is widely expressed in both fetal and adult tissues and acts as a tumor suppressor. Here, we demonstrate the molecular mechanism through which VHL inhibits the Hedgehog-Gli pathway. VHL decreased Gli1-mediated promoter transactivation as well as the expression of Hedgehog/Gli pathway target genes. Nuclear translocation of cytosolic Gli1 protein was inhibited by VHL via protein-protein interaction. These results indicate that overexpression of VHL may antagonize Hedgehog-Gli activation at the post-translational level in Hedgehog pathway-induced cancers.
authors: Department of Molecular Biology, College of Natural Sciences, Pusan National University, Busan 609-735, Republic of Korea.
authors: Hyun Kook
authors: HK
authors: Cho
authors: So Young
authors: SY
authors: Kim
authors: Kook Hwan
authors: KH
authors: Kim
authors: Hyeong Hoe
authors: HH
authors: Kim
authors: JaeHun
authors: J
authors: Cheong
mesh_terms: D021581:Active Transport, Cell Nucleus; D000818:Animals; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism; D057809:HEK293 Cells; D053823:Hedgehog Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008856:Microscopy, Fluorescence; D041681:NIH 3T3 Cells; D011485:Protein Binding; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D051794:Von Hippel-Lindau Tumor Suppressor Protein / Q000235:genetics / Q000378:metabolism*; D000071676:Zinc Finger Protein GLI1
chemical_list: C400551:GLI1 protein, human; D053823:Hedgehog Proteins; D008164:Luminescent Proteins; D014157:Transcription Factors; D000071676:Zinc Finger Protein GLI1; D051794:Von Hippel-Lindau Tumor Suppressor Protein; C497446:VHL protein, human