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Nuclear Actin Regulates Dynamic Subcellular Localization and Activity of the SRF Cofactor MAL
Maria K. Vartiainen,1*Sebastian Guettler,1*Banafshe Larijani,2Richard Treisman1
Actin, which is best known as a cytoskeletal component, alsoparticipates in the control of gene expression. We report afunction of nuclear actin in the regulation of MAL, a coactivatorof the transcription factor serum response factor (SRF). MAL,which binds monomeric actin, is cytoplasmic in many cells butaccumulates in the nucleus upon serum-induced actin polymerization.MAL rapidly shuttles between cytoplasm and nucleus in unstimulatedcells. Serum stimulation effectively blocks MAL nuclear export,which requires MAL-actin interaction. Nuclear MAL binds SRFtarget genes but remains inactive unless actin binding is disrupted.Fluorescence resonance energy transfer analysis demonstratesthat the MAL-actin interaction responds to extracellular signals.Serum-induced signaling is thus communicated to nuclear actinto 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.
To whom correspondence should be addressed. E-mail: Richard.Treisman{at}cancer.org.uk
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