Raf 1 represses expression of the tight junction protein occludin via activation of the zinc-finger transcription factor slug.

Raf 1 represses expression of the tight junction protein occludin via activation of the zinc-finger transcription factor slug. Research Abstract Details 

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Raf 1 represses expression of the tight junction protein occludin via activation of the zinc-finger transcription factor slug. Abstract Text:

Z Wang,P Wade,K J Mandell,A Akyildiz,C A Parkos,R J Mrsny,A Nusrat,

Although dysregulation of tight junction (TJ) proteins is observed in epithelial malignancy, their participation in epithelial transformation is poorly understood. Recently we demonstrated that expression of oncogenic Raf 1 in Pa4 epithelial cells disrupts TJs and induces an oncogenic phenotype by downregulating expression of the TJ protein, occludin. Here we report the mechanism by which Raf 1 regulates occludin expression. Raf 1 inhibited occludin transcription by repressing a minimal segment of the occludin promoter in concert with upregulation of the transcriptional repressor, Slug without influencing the well-documented transcriptional repressor, Snail. Overexpression of Slug in Pa4 cells recapitulated the effect of Raf 1 on occludin expression, and depletion of Slug by small interfering RNA abrogated the effect of Raf 1 on occludin. Finally, chromatin immunoprecipitation assays and site-directed mutagenesis demonstrated a direct interaction between Slug and an E-box within the minimal Raf 1-responsive segment of the occludin promoter. These findings support a role of Slug in mediating Raf 1-induced transcriptional repression of occludin and subsequent epithelial to mesenchymal transition.

Raf 1 represses expression of the tight junction protein occludin via activation of the zinc-finger transcription factor slug. Publishing Authors By Initials

Z Wang,P Wade,KJ Mandell,A Akyildiz,CA Parkos,RJ Mrsny,A Nusrat,

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Raf 1 represses expression of the tight junction protein occludin via activation of the zinc-finger transcription factor slug. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Oncogene

VOLUME: 26

Page Numbers: 1222-30

Journal Abbreviation: Oncogene

ISSN: 0950-9232

DAY: 21

MONTH: 08

YEAR: 2006

Raf 1 represses expression of the tight junction protein occludin via activation of the zinc-finger transcription factor slug. Information

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LANGUAGE: eng

NlmUniqueID: 8711562

Raf 1 represses expression of the tight junction protein occludin via activation of the zinc-finger transcription factor slug. Keywords Mesh Terms:

KEYWORDS: Zinc Fingers

MESH TERMS: metabolism

Chemical & Substance for Abstract: Raf 1 represses expression of the tight junction protein occludin via activation of the zinc-finger transcription factor slug. Information

Substance Name: Proto-Oncogene Proteins c-raf

Registry Number: EC 2.7.1.37

Grant and Affiliation Information for Raf 1 represses expression of the tight junction protein occludin via activation of the zinc-finger transcription factor slug.

AFFILIATION: Epithelial Pathobiology Research Unit, Department of Pathology, Emory University, Atlanta, GA 30322, USA.

Country: England

AGENCY: United States NIDDK

GRANT: DK 61379

ACRONYM: DK

MEDLINETA: Oncogene

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