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First published online 7 November 2006
doi: 10.1242/jcs.03257

Journal of Cell Science 119, 4850-4856 (2006)
Published by The Company of Biologists 2006
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Research Article

ß-catenin relieves I-mfa-mediated suppression of LEF-1 in mammalian cells

Weijun Pan*, Yingying Jia*, Tao Huang, Jiyong Wang, Donglei Tao, Xiaoqing Gan and Lin Li{ddagger}

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

{ddagger} Author for correspondence (e-mail: lli{at}sibs.ac.cn)

Accepted 30 August 2006

We have previously shown that ß-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 ß-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 ß-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 ß-catenin levels, which in turn relieve I-mfa-mediated suppression.

Key words: Wnt, ß-catenin, I-mfa, LEF-1, Myogenesis, P19 carcinoma stem cells


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