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Science 316 (5832): 1749-1752

Copyright © 2007 by the American Association for the Advancement of Science

Nuclear Actin Regulates Dynamic Subcellular Localization and Activity of the SRF Cofactor MAL

Maria K. Vartiainen,1* Sebastian Guettler,1* Banafshe Larijani,2 Richard Treisman1{dagger}

Abstract: Actin, which is best known as a cytoskeletal component, also participates in the control of gene expression. We report a function of nuclear actin in the regulation of MAL, a coactivator of the transcription factor serum response factor (SRF). MAL, which binds monomeric actin, is cytoplasmic in many cells but accumulates in the nucleus upon serum-induced actin polymerization. MAL rapidly shuttles between cytoplasm and nucleus in unstimulated cells. Serum stimulation effectively blocks MAL nuclear export, which requires MAL-actin interaction. Nuclear MAL binds SRF target genes but remains inactive unless actin binding is disrupted. Fluorescence resonance energy transfer analysis demonstrates that the MAL-actin interaction responds to extracellular signals. Serum-induced signaling is thus communicated to nuclear actin to control a transcriptional regulator.

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

* These authors contributed equally to this work.

{dagger} To whom correspondence should be addressed. E-mail: Richard.Treisman{at}cancer.org.uk

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