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Molecular and Cellular Biology, January 2008, p. 732-742, Vol. 28, No. 2
0270-7306/08/$08.00+0     doi:10.1128/MCB.01623-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

RPEL Motifs Link the Serum Response Factor Cofactor MAL but Not Myocardin to Rho Signaling via Actin Binding ^,

Sebastian Guettler,¹ Maria K. Vartiainen,^1, Francesc Miralles,^1, Banafshe Larijani,² and Richard Treisman^1*

Transcription,¹ Cell Biophysics Laboratories, Cancer Research UK London Research Institute, Lincoln's Inn Fields Laboratories, 44 Lincoln's Inn Fields, London WC2A 3PX, United Kingdom²

Received 3 September 2007/ Returned for modification 24 October 2007/ Accepted 2 November 2007

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.

Published ahead of print on 19 November 2007.

Supplemental material for this article may be found at http://mcb.asm.org/.

Present address: Institute of Biotechnology, University of Helsinki, Viikinkaari 9, Helsinki 00014, Finland.

Present address: Basic Medical Sciences Division, St. George's Hospital, University of London Medical School, Cranmer Terrace, London SW17 0RE, United Kingdom.

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