title: Beta-catenin relieves I-mfa-mediated suppression of LEF-1 in mammalian cells.
abstract: We have previously shown that beta-catenin interacts with a transcription suppressor I-mfa and, through this interaction, canonical Wnt signaling could relieve I-mfa-mediated suppression of myogenic regulatory factors (MRFs). In this study, we found that, based on this interaction, I-mfa-mediated suppression of the Wnt transcription factor T-cell factor/lymphoid enhancing factor-1 (TCF/LEF-1) can also be relieved. Our work showed that knocking down endogenous I-mfa expression mimics canonical Wnt treatment by inducing myogenesis and increasing Wnt reporter gene activity, endogenous Wnt target gene expression and expression of MRFs in P19 cells. More importantly, these I-mfa small interfering RNA (siRNA)-induced effects could be blocked by a dominant-negative mutant of LEF-1, confirming the involvement of the TCF/LEF-1 pathway. In addition, we found that beta-catenin could compete with I-mfa for binding to LEF-1 and relieve the inhibitory effects of I-mfa in overexpression systems. Furthermore, canonical Wnt was able to reduce the levels of endogenous I-mfa associated with LEF-1, while increasing that of I-mfa associated with beta-catenin. All of the evidence supports a conclusion that I-mfa can suppress myogenesis by inhibiting TCF/LEF-1 and that canonical Wnt signaling may relieve the suppression through elevating beta-catenin levels, which in turn relieve I-mfa-mediated suppression.
authors.affiliation: State Key Laboratory of Molecular Biology and Center of Cell Signaling, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Weijun
authors.initials: W
authors.lastname: Pan
authors.forename: Yingying
authors.initials: Y
authors.lastname: Jia
authors.forename: Tao
authors.initials: T
authors.lastname: Huang
authors.forename: Jiyong
authors.initials: J
authors.lastname: Wang
authors.forename: Donglei
authors.initials: D
authors.lastname: Tao
authors.forename: Xiaoqing
authors.initials: X
authors.lastname: Gan
authors.forename: Lin
authors.initials: L
authors.lastname: Li
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D006801:Humans; D051821:Lymphoid Enhancer-Binding Factor 1 / Q000378:metabolism*; D051379:Mice; D008954:Models, Biological; D024510:Muscle Development / Q000187:drug effects; D050505:Mutant Proteins / Q000378:metabolism; D018006:Myogenic Regulatory Factors / Q000378:metabolism* / Q000502:physiology; D041681:NIH 3T3 Cells; D011485:Protein Binding; D034741:RNA, Small Interfering / Q000494:pharmacology; D014162:Transfection; D051153:Wnt Proteins / Q000378:metabolism; D060508:Wnt3 Protein; D051176:beta Catenin / Q000378:metabolism / Q000502:physiology*
chemical_list: D051821:Lymphoid Enhancer-Binding Factor 1; D050505:Mutant Proteins; D018006:Myogenic Regulatory Factors; D034741:RNA, Small Interfering; D051153:Wnt Proteins; D060508:Wnt3 Protein; D051176:beta Catenin; C101295:MDFI protein, human