title: Rab23 negatively regulates Gli1 transcriptional factor in a Su(Fu)-dependent manner.
abstract: Hedgehog (Hh) signaling, via the key signal transducer Smoothened (SMO) and Gli transcription factors, is essential for embryonic development and carcinogenesis. While the biological relevance of hedgehog signaling to cancer is well established, very little is known about the molecular mechanisms by which signaling transduction of this pathway occurs. Rab23 was discovered as a negative regulator of the Hh pathway through a mouse genetic study. Here we report that Rab23 directly associates with Su(Fu) and inhibits Gli1 function in a Su(Fu)-dependent manner. By confocal microscope and immunoprecipitation, we detected interaction between Rab23 and Su(Fu). Using Gli1-mediated reporter gene analysis, we found that Rab23 can suppress Gli1 transcriptional activity in wild type but not Su(Fu) null fibroblasts. Similarly, Rab23 expression reduced the nuclear localization of Gli1 in wild type but not Su(Fu) null fibroblast cells. Consistent with the GTPase motif in the protein, we showed that Rab23 has GTPase activity. The dominant negative form of Rab23 was unable to suppress Gli1-mediated transcriptional activity. Taken together, these data provide evidence to support that Rab23 negatively regulates Gli1 activity in a Su(Fu)-dependent manner.
authors.affiliation: Wells Center for Pediatric Research, Department of Pediatrics, Indiana University, 980 W. Walnut St., Indianapolis, IN 46202, USA.
authors.forename: Sumin
authors.initials: S
authors.lastname: Chi
authors.forename: Guorui
authors.initials: G
authors.lastname: Xie
authors.forename: Hailan
authors.initials: H
authors.lastname: Liu
authors.forename: Kai
authors.initials: K
authors.lastname: Chen
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Zhang
authors.forename: Chengxin
authors.initials: C
authors.lastname: Li
authors.forename: Jingwu
authors.initials: J
authors.lastname: Xie
mesh_terms: D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D053823:Hedgehog Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051379:Mice; D041681:NIH 3T3 Cells; D021381:Protein Transport; D012097:Repressor Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D014157:Transcription Factors / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation; D014162:Transfection; D000071676:Zinc Finger Protein GLI1; D020691:rab GTP-Binding Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*
chemical_list: C400551:GLI1 protein, human; D053823:Hedgehog Proteins; D012097:Repressor Proteins; C490764:SUFU protein, human; D014157:Transcription Factors; D000071676:Zinc Finger Protein GLI1; C486614:RAB23 protein, human; D020691:rab GTP-Binding Proteins