RPEL motifs link the serum response factor cofactor MAL but not myocardin to Rho signaling via actin binding

Sebastian Guettler, Maria K. Vartiainen, Francesc Miralles, Banafshe Larijani, Richard Treisman

Research output: Contribution to journalArticlepeer-review

128 Citations (SciVal)


Myocardin (MC) family proteins are transcriptional coactivators for serum response factor (SRF). Each family member possesses a conserved N-terminal region containing three RPEL motifs (the "RPEL domain"). MAL/MKL1/myocardin-related transcription factor A is cytoplasmic, accumulating in the nucleus upon activation of Rho GTPase signaling, which alters interactions between G-actin and the RPEL domain. We demonstrate that MC, which is nuclear, does not shuttle through the cytoplasm and that the contrasting nucleocytoplasmic shuttling properties of MAL and MC are defined by their RPEL domains. We show that the MAL RPEL domain binds actin more avidly than that of MC and that the RPEL motif itself is an actin-binding element. RPEL1 and RPEL2 of MC bind actin weakly compared with those of MAL, while RPEL3 is of comparable and low affinity in the two proteins. Actin binding by all three motifs is required for MAL regulation. The differing behaviors of MAL and MC are specified by the RPEL1-RPEL2 unit, while RPEL3 can be exchanged between them. We propose that differential actin occupancy of multiple RPEL motifs regulates nucleocytoplasmic transport and activity of MAL.

Original languageEnglish
Pages (from-to)732-742
Number of pages11
JournalMolecular and Cellular Biology
Issue number2
Early online date19 Nov 2007
Publication statusPublished - 1 Jan 2008

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology


Dive into the research topics of 'RPEL motifs link the serum response factor cofactor MAL but not myocardin to Rho signaling via actin binding'. Together they form a unique fingerprint.

Cite this