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Mol. Cell. Biol., Aug 1997, 4750-4760, Vol 17, No. 8
Y Kong, MJ Flick, AJ Kudla and SF Konieczny
The muscle LIM protein (MLP) is a muscle-specific LIM-only factor that
exhibits a dual subcellular localization, being present in both the nucleus
and in the cytoplasm. Overexpression of MLP in C2C12 myoblasts enhances
skeletal myogenesis, whereas inhibition of MLP activity blocks terminal
differentiation. Thus, MLP functions as a positive developmental regulator,
although the mechanism through which MLP promotes terminal differentiation
events remains unknown. While examining the distinct roles associated with
the nuclear and cytoplasmic forms of MLP, we found that nuclear MLP
functions through a physical interaction with the muscle basic
helix-loop-helix (bHLH) transcription factors MyoD, MRF4, and myogenin.
This interaction is highly specific since MLP does not associate with
nonmuscle bHLH proteins E12 or E47 or with the myocyte enhancer factor-2
(MEF2) protein, which acts cooperatively with the myogenic bHLH proteins to
promote myogenesis. The first LIM motif in MLP and the highly conserved
bHLH region of MyoD are responsible for mediating the association between
these muscle-specific factors. MLP also interacts with MyoD-E47
heterodimers, leading to an increase in the DNA-binding activity associated
with this active bHLH complex. Although MLP lacks a functional
transcription activation domain, we propose that it serves as a cofactor
for the myogenic bHLH proteins by increasing their interaction with
specific DNA regulatory elements. Thus, the functional complex of
MLP-MyoD-E protein reveals a novel mechanism for both initiating and
maintaining the myogenic program and suggests a global strategy for how
LIM-only proteins may control a variety of developmental pathways.
Copyright © 1997, American Society for Microbiology
Muscle LIM protein promotes myogenesis by enhancing the activity of MyoD
Department of Biological Sciences, Purdue University, West Lafayette, Indiana 47907-1392, USA.
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