The LIM-only protein FHL2 interacts with {beta}-catenin and promotes differentiation of mouse myoblasts

doi:10.1083/jcb.200202075

Published online 7 October 2002. doi:10.1083/jcb.200202075

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© The Rockefeller University Press, 0021-9525/2002/10/113 $5.00
The Journal of Cell Biology, Volume 159, Number 1, 113-122

Article

The LIM-only protein FHL2 interacts with ß-catenin and promotes differentiation of mouse myoblasts

Bernd Martin¹, Richard Schneider¹, Stefanie Janetzky², Zoe Waibler¹, Petra Pandur⁴, Michael Kühl⁴, Jürgen Behrens³, Klaus von der Mark², Anna Starzinski-Powitz¹ and Viktor Wixler²

¹ Institut der Anthropologie und Humangenetik für Biologen, Johann-Wolfgang-Goethe-Universität, 60323 Frankfurt, Germany
² Lehrstuhl für Experimentelle Medizin I, Nikolaus-Fiebiger-Zentrum für Molekulare Medizin, Friedrich-Alexander Universität Erlangen/Nürnberg, 91054 Erlangen, Germany
³ Lehrstuhl für Experimentelle Medizin II, Nikolaus-Fiebiger-Zentrum für Molekulare Medizin, Friedrich-Alexander Universität Erlangen/Nürnberg, 91054 Erlangen, Germany
⁴ Abteilung für Biochemie, Medizinische Fakultät der Universität Ulm, 89069 Ulm, Germany

Address correspondence to Viktor Wixler, Lehrstuhl für Experimentelle Medizin I, Nikolaus-Fiebiger Zentrum für Molekulare Medizin, Friedrich-Alexander Universität Erlangen/Nürnberg, Glückstr. 6, 91054 Erlangen, Germany. Tel.: 49-9131-852-6925. Fax: 49-9131-852-6341. E-mail: vwixler{at}molmed.uni-erlangen.de

FHL2 is a LIM-domain protein expressed in myoblasts but down-regulatedin malignant rhabdomyosarcoma cells, suggesting an importantrole of FHL2 in muscle development. To investigate the importanceof FHL2 during myoblast differentiation, we performed a yeasttwo-hybrid screen using a cDNA library derived from myoblastsinduced for differentiation. We identified ß-cateninas a novel interaction partner of FHL2 and confirmed the specificityof association by direct in vitro binding tests and coimmunoprecipitationassays from cell lysates. Deletion analysis of both proteinsrevealed that the NH₂-terminal part of ß-catenin issufficient for binding in yeast, but addition of the first armadillorepeat is necessary for binding FHL2 in mammalian cells, whereasthe presence of all four LIM domains of FHL2 is needed for theinteraction. Expression of FHL2 counteracts ß-catenin–mediatedactivation of a TCF/LEF-dependent reporter gene in a dose-dependentand muscle cell–specific manner. After injection intoXenopus embryos, FHL2 inhibited the ß-catenin–inducedaxis duplication. C2C12 mouse myoblasts stably expressing FHL2show increased myogenic differentiation reflected by acceleratedmyotube formation and expression of muscle-specific proteins.These data imply that FHL2 is a muscle-specific repressor ofLEF/TCF target genes and promotes myogenic differentiation byinteracting with ß-catenin.

Key Words: FHL2; repression of transcription; DRAL; myogenic differentiation; ß-catenin–TCF complex

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