title: Nuclear actin regulates dynamic subcellular localization and activity of the SRF cofactor MAL.
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.
authors.affiliation: Transcription Laboratory, Cancer Research UK, London Research Institute, Lincoln's Inn Fields Laboratories, 44 Lincoln's Inn Fields, London WC2A 3PX, UK.
authors.forename: Maria K
authors.initials: MK
authors.lastname: Vartiainen
authors.forename: Sebastian
authors.initials: S
authors.lastname: Guettler
authors.forename: Banafshe
authors.initials: B
authors.lastname: Larijani
authors.forename: Richard
authors.initials: R
authors.lastname: Treisman
mesh_terms: D016475:3T3 Cells; D000199:Actins / Q000502:physiology*; D021581:Active Transport, Cell Nucleus; D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism; D031541:Fluorescence Resonance Energy Transfer; D005786:Gene Expression Regulation; D049452:Green Fluorescent Proteins; D051379:Mice; D011485:Protein Binding; D015534:Trans-Activators / Q000378:metabolism*
chemical_list: D000199:Actins; C511173:Mrtfa protein, mouse; D015534:Trans-Activators; D049452:Green Fluorescent Proteins