Two novel members of the ABLIM protein family, ABLIM-2 and -3, associate with STARS and directly bind F-actin.
In addition to regulating cell motility, contractility, and cytokinesis, the actin cytoskeleton plays a critical role in the regulation of transcription and gene expression. We have previously identified a novel muscle-specific actin-binding protein, STARS (striated muscle activator of Rho signaling), which directly binds actin and stimulates serum-response factor (SRF)-dependent transcription. ... To further dissect the STARS/SRF pathway, we performed a yeast two-hybrid screen of a skeletal muscle cDNA library using STARS as bait, and we identified two novel members of the ABLIM protein family, ABLIM-2 and -3, as STARS-interacting proteins. ABLIM-1, which is expressed in retina, brain, and muscle tissue, has been postulated to function as a tumor suppressor. ABLIM-2 and -3 display distinct tissue-specific expression patterns with the highest expression levels in muscle and neuronal tissue. Moreover, these novel ABLIM proteins strongly bind F-actin, are localized to actin stress fibers, and synergistically enhance STARS-dependent activation of SRF. Conversely, knockdown of endogenous ABLIM expression utilizing small interfering RNA significantly blunted SRF-dependent transcription in C2C12 skeletal muscle cells. These findings suggest that the members of the novel ABLIM protein family may serve as a scaffold for signaling modules of the actin cytoskeleton and thereby modulate transcription.
Mesh Terms:
Actins, Amino Acid Sequence, Animals, COS Cells, Cercopithecus aethiops, Humans, Mice, Microfilament Proteins, Molecular Sequence Data, Muscle, Skeletal, Protein Binding, Retina, Sequence Homology, Amino Acid, Signal Transduction, Two-Hybrid System Techniques
Actins, Amino Acid Sequence, Animals, COS Cells, Cercopithecus aethiops, Humans, Mice, Microfilament Proteins, Molecular Sequence Data, Muscle, Skeletal, Protein Binding, Retina, Sequence Homology, Amino Acid, Signal Transduction, Two-Hybrid System Techniques
J. Biol. Chem.
Date: Mar. 16, 2007
PubMed ID: 17194709
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