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Publication : The cytoskeleton-associated PDZ-LIM protein, ALP, acts on serum response factor activity to regulate muscle differentiation.

First Author  Pomiès P Year  2007
Journal  Mol Biol Cell Volume  18
Issue  5 Pages  1723-33
PubMed ID  17332502 Mgi Jnum  J:127476
Mgi Id  MGI:3763799 Doi  10.1091/mbc.E06-09-0815
Citation  Pomies P, et al. (2007) The cytoskeleton-associated PDZ-LIM protein, ALP, acts on serum response factor activity to regulate muscle differentiation. Mol Biol Cell 18(5):1723-33
abstractText  In this report, an antisense RNA strategy has allowed us to show that disruption of ALP expression affects the expression of the muscle transcription factors myogenin and MyoD, resulting in the inhibition of muscle differentiation. Introduction of a MyoD expression construct into ALP-antisense cells is sufficient to restore the capacity of the cells to differentiate, illustrating that ALP function occurs upstream of MyoD. It is known that MyoD is under the control of serum response factor (SRF), a transcriptional regulator whose activity is modulated by actin dynamics. A dramatic reduction of actin filament bundles is observed in ALP-antisense cells and treatment of these cells with the actin-stabilizing drug jasplakinolide stimulates SRF activity and restores the capacity of the cells to differentiate. Furthermore, we show that modulation of ALP expression influences SRF activity, the level of its coactivator, MAL, and muscle differentiation. Collectively, these results suggest a critical role of ALP on muscle differentiation, likely via cytoskeletal regulation of SRF.
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