Coactivation of MEF2 by the SAP domain proteins myocardin and MASTR.
Myocardin is a cardiac- and smooth muscle-specific SAP domain transcription factor that functions as a coactivator for serum response factor (SRF), which controls genes involved in muscle differentiation and cell proliferation. The DNA binding domain of SRF, which interacts with myocardin, shares homology with the MEF2 transcription factor, which also controls muscle and growth-associated genes. Here we show that alternative splicing produces a cardiac-enriched isoform of myocardin containing a unique peptide sequence that confers the ability to interact with and stimulate the transcriptional activity of MEF2. This MEF2 binding motif is also contained in a previously unknown SAP domain transcription factor, referred to as MASTR, which functions as a MEF2 coactivator. This unique protein-protein interaction motif expands the regulatory potential of myocardin, and its presence in MASTR reveals a new mechanism for the control of MEF2 activity.
Creemers
Esther E
EE
Department of Molecular Biology, University of Texas Southwestern Medical Center, 6000 Harry Hines Boulevard, Dallas, 75390, USA.
Sutherland
Lillian B
LB
Oh
Jiyeon
J
Barbosa
Ana C
AC
Olson
Eric N
EN
D051696:Activating Transcription Factors / Q000502:physiology; D017398:Alternative Splicing; D000818:Animals; D001483:Base Sequence; D006801:Humans; D026161:MADS Domain Proteins / Q000378:metabolism*; D064326:MEF2 Transcription Factors; D051379:Mice; D008969:Molecular Sequence Data; D018006:Myogenic Regulatory Factors / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism*; D011485:Protein Binding; D020033:Protein Isoforms / Q000378:metabolism; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid; D015534:Trans-Activators / Q000235:genetics* / Q000378:metabolism*; D000099251:Myocardin
D051696:Activating Transcription Factors; D026161:MADS Domain Proteins; D064326:MEF2 Transcription Factors; D018006:Myogenic Regulatory Factors; D009687:Nuclear Proteins; D020033:Protein Isoforms; D015534:Trans-Activators; D000099251:Myocardin; C512516:MASTR protein, mouse; C578035:MEF2A protein, human