title: Sox4 stimulates ß-catenin activity through induction of CK2.
abstract: ß-catenin is a key component of the Wnt signaling pathway and the abnormal accumulation of ß-catenin is characteristic of various types of cancer. Here we demonstrate that overexpression of Sox4 enhances ß-catenin/TCF activity by increasing the stability of ß-catenin. Sox4 increased the protein level of ß-catenin and its target gene cyclin D1 in a dose-dependent manner. An siRNA experiment for Sox4 also demonstrated that Sox4 increases the protein levels of ß-catenin and thus activates the Wnt signaling pathway. We found that induction of ß-catenin/TCF activity by Sox4 is caused by stabilization of the ß-catenin protein, but not by induction of ß-catenin transcription. We further demonstrate that the increased level of ß-catenin is caused by induction of CK2. In light of recent evidence that Sox4 expression is activated in the colon and in other tumors with ß-catenin dysregulation, our findings suggest that Sox4 acts as an agonist of Wnt signaling in cancer cells.
authors.affiliation: Department of Biochemistry, Dongguk University College of Oriental Medicine, Gyeongju 780-714, Republic of Korea.
authors.forename: Ae-Kyung
authors.initials: AK
authors.lastname: Lee
authors.forename: Sang-Gun
authors.initials: SG
authors.lastname: Ahn
authors.forename: Jung-Hoon
authors.initials: JH
authors.lastname: Yoon
authors.forename: Soo-A
authors.initials: SA
authors.lastname: Kim
mesh_terms: D047390:Casein Kinase II / Q000096:biosynthesis* / Q000378:metabolism; D002478:Cells, Cultured; D056741:Cyclin D / Q000235:genetics / Q000378:metabolism; D004790:Enzyme Induction / Q000187:drug effects / Q000502:physiology; D015870:Gene Expression / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D034741:RNA, Small Interfering / Q000494:pharmacology; D055751:SOXC Transcription Factors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D014162:Transfection; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics; D051153:Wnt Proteins / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism*
chemical_list: D056741:Cyclin D; D034741:RNA, Small Interfering; C083431:SOX4 protein, human; D055751:SOXC Transcription Factors; D051153:Wnt Proteins; D051176:beta Catenin; D047390:Casein Kinase II