Rab23 negatively regulates Gli1 transcriptional factor in a Su(Fu)-dependent manner

Sumin Chi, Guorui Xie, Hailan Liu, Kai Chen, Xiaoli Zhang, Chengxin Li, Jingwu Xie

Research output: Contribution to journalArticle

27 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1222-1228
Number of pages7
JournalCellular Signalling
Volume24
Issue number6
DOIs
StatePublished - Jun 2012

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Hedgehogs
GTP Phosphohydrolases
Fibroblasts
Null Lymphocytes
Amino Acid Motifs
Transducers
Reporter Genes
Immunoprecipitation
Embryonic Development
Carcinogenesis
Transcription Factors
Neoplasms

Keywords

  • Gli1
  • Hedgehog
  • Rab23

ASJC Scopus subject areas

  • Cell Biology

Cite this

Rab23 negatively regulates Gli1 transcriptional factor in a Su(Fu)-dependent manner. / Chi, Sumin; Xie, Guorui; Liu, Hailan; Chen, Kai; Zhang, Xiaoli; Li, Chengxin; Xie, Jingwu.

In: Cellular Signalling, Vol. 24, No. 6, 06.2012, p. 1222-1228.

Research output: Contribution to journalArticle

Chi, Sumin ; Xie, Guorui ; Liu, Hailan ; Chen, Kai ; Zhang, Xiaoli ; Li, Chengxin ; Xie, Jingwu. / Rab23 negatively regulates Gli1 transcriptional factor in a Su(Fu)-dependent manner. In: Cellular Signalling. 2012 ; Vol. 24, No. 6. pp. 1222-1228.
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