Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.
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
The editors suggest the following Related Resources on Science sites:
In Science Magazine
PERSPECTIVES
Jiang I. Wu and Gerald R. Crabtree (22 June 2007) Science316 (5832), 1710.
[DOI: 10.1126/science.1145014] |Summary »|Full Text »|PDF »
In Science Signaling
EDITORS' CHOICE
Beverly A. Purnell (26 June 2007) Sci. STKE2007 (392), tw222.
[DOI: 10.1126/stke.3922007tw222] |Abstract »
THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Effect of destrin mutations on the gene expression profile in vivo.
A. M. Verdoni, N. Aoyama, A. Ikeda, and S. Ikeda (2008)
Physiol Genomics
34, 9-21
|Abstract »|Full Text »|PDF »
Role of Porphyromonas gingivalis SerB in Gingival Epithelial Cell Cytoskeletal Remodeling and Cytokine Production.
Y. Hasegawa, G. D. Tribble, H. V. Baker, J. J. Mans, M. Handfield, and R. J. Lamont (2008)
Infect. Immun.
76, 2420-2427
|Abstract »|Full Text »|PDF »
MKL1 mediates TGF-{beta}1-induced {alpha}-smooth muscle actin expression in human renal epithelial cells.
G. Elberg, L. Chen, D. Elberg, M. D. Chan, C. J. Logan, and M. A. Turman (2008)
Am J Physiol Renal Physiol
294, F1116-F1128
|Abstract »|Full Text »|PDF »
Epithelial cell-cell contacts regulate SRF-mediated transcription via Rac-actin-MAL signalling.
S. Busche, A. Descot, S. Julien, H. Genth, and G. Posern (2008)
J. Cell Sci.
121, 1025-1035
|Abstract »|Full Text »|PDF »
As functional nuclear actin comes into view, is it globular, filamentous, or both?.
Proteomic analysis of human omental adipose tissue in the polycystic ovary syndrome using two-dimensional difference gel electrophoresis and mass spectrometry.
M. Corton, J. I. Botella-Carretero, J. A. Lopez, E. Camafeita, J. L. San Millan, H. F. Escobar-Morreale, and B. Peral (2008)
Hum. Reprod.
23, 651-661
|Abstract »|Full Text »|PDF »
Drosophila sticky/citron kinase Is a Regulator of Cell-Cycle Progression, Genetically Interacts With Argonaute 1 and Modulates Epigenetic Gene Silencing.
Functional interactions between phosphatase POPX2 and mDia modulate RhoA pathways.
Y. Xie, E-J. Tan, S. Wee, E. Manser, L. Lim, and C.-G. Koh (2008)
J. Cell Sci.
121, 514-521
|Abstract »|Full Text »|PDF »
Sequences in Intron 51 of the von Willebrand Factor Gene Target Promoter Activation to a Subset of Lung Endothelial Cells in Transgenic Mice.
A. M. Kleinschmidt, M. Nassiri, M. S. Stitt, K. Wasserloos, S. C. Watkins, B. R. Pitt, and N. Jahroudi (2008)
J. Biol. Chem.
283, 2741-2750
|Abstract »|Full Text »|PDF »
RPEL Motifs Link the Serum Response Factor Cofactor MAL but Not Myocardin to Rho Signaling via Actin Binding.
S. Guettler, M. K. Vartiainen, F. Miralles, B. Larijani, and R. Treisman (2008)
Mol. Cell. Biol.
28, 732-742
|Abstract »|Full Text »|PDF »
Dual roles of myocardin-related transcription factors in epithelial mesenchymal transition via slug induction and actin remodeling.