Wnt signaling stimulates transcriptional outcome of the Hedgehog pathway by stabilizing GLI1 mRNA.
Wnt and Hedgehog signaling pathways play central roles in embryogenesis, stem cell maintenance, and tumorigenesis. However, the mechanisms by which these two pathways interact are not well understood. Here, we identified a novel mechanism by which Wnt signaling pathway stimulates the transcriptional output of Hedgehog signaling. Wnt/beta-catenin signaling induces expression of an RNA-binding protein, CRD-BP, which in turn binds and stabilizes GLI1 mRNA, causing an elevation of GLI1 expression and transcriptional activity. The newly described mode of regulation of GLI1 seems to be important to several functions of Wnt, including survival and proliferation of colorectal cancer cells.
Noubissi
Felicite K
FK
Department of Dermatology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin 53706, USA.
Goswami
Srikanta
S
Sanek
Nicholas A
NA
Kawakami
Kazuyuki
K
Minamoto
Toshinari
T
Moser
Amy
A
Grinblat
Yevgenya
Y
Spiegelman
Vladimir S
VS
D000818:Animals; D002460:Cell Line; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D053823:Hedgehog Proteins / Q000378:metabolism*; D006801:Humans; D012333:RNA, Messenger; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics*; D014158:Transcription, Genetic; D014162:Transfection; D051153:Wnt Proteins / Q000378:metabolism*; D015027:Zebrafish; D000071676:Zinc Finger Protein GLI1; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism
C400551:GLI1 protein, human; D053823:Hedgehog Proteins; C406144:IGF2BP1 protein, human; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D014157:Transcription Factors; D051153:Wnt Proteins; D000071676:Zinc Finger Protein GLI1; D051176:beta Catenin