Beta-catenin relieves I-mfa-mediated suppression of LEF-1 in mammalian cells.
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.
Pan
Weijun
W
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.
Jia
Yingying
Y
Huang
Tao
T
Wang
Jiyong
J
Tao
Donglei
D
Gan
Xiaoqing
X
Li
Lin
L
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*
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