A new mechanism of SOX9 action to regulate PKCalpha expression in the intestine epithelium.
Variations of protein kinase C (PKC) expression greatly influence the proliferation-to-differentiation transition (PDT) of intestinal epithelial cells and might have an important impact on intestinal tumorigenesis. We demonstrate here that the expression of PKCalpha in proliferating intestinal epithelial cells is repressed both in vitro and in vivo by the SOX9 transcription factor. This repression does not require DNA binding of the SOX9 high-mobility group (HMG) domain but is mediated through a new mechanism of SOX9 action requiring the central and highly conserved region of SOXE members. Because SOX9 expression is itself upregulated by Wnt-APC signaling in intestinal epithelial cells, the present study points out this transcription factor as a molecular link between the Wnt-APC pathway and PKCalpha. These results provide a potential explanation for the decrease of PKCalpha expression in colorectal cancers with constitutive activation of the Wnt-APC pathway.
Dupasquier
Sébastien
S
CNRS, UMR 5203, Institut de Génomique Fonctionnelle, 34094, Montpellier, France.
Abdel-Samad
Rana
R
Glazer
Robert I
RI
Bastide
Pauline
P
Jay
Philippe
P
Joubert
Dominique
D
Cavaillès
Vincent
V
Blache
Philippe
P
Quittau-Prévostel
Corinne
C
D025601:Adenomatous Polyposis Coli Protein / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D007413:Intestinal Mucosa / Q000166:cytology / Q000378:metabolism*; D051571:Protein Kinase C-alpha / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D055758:SOX9 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D016329:Sp1 Transcription Factor / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D051153:Wnt Proteins / Q000378:metabolism
D025601:Adenomatous Polyposis Coli Protein; D034741:RNA, Small Interfering; D055758:SOX9 Transcription Factor; D016329:Sp1 Transcription Factor; D051153:Wnt Proteins; D051571:Protein Kinase C-alpha