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Mutant actins that stabilise F-actin use distinct mechanisms to activate the SRF coactivator MAL.

Posern, G; Miralles, F; Guettler, S; Treisman, R (2004) Mutant actins that stabilise F-actin use distinct mechanisms to activate the SRF coactivator MAL. EMBO J, 23 (20). 3973 - 3983 . ISSN 0261-4189 https://doi.org/10.1038/sj.emboj.7600404
SGUL Authors: Miralles Arenas, Francisco

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Abstract

Nuclear accumulation of the serum response factor coactivator MAL/MKL1 is controlled by its interaction with G-actin, which results in its retention in the cytoplasm in cells with low Rho activity. We previously identified actin mutants whose expression promotes MAL nuclear accumulation via an unknown mechanism. Here, we show that actin interacts directly with MAL in vitro with high affinity. We identify a further activating mutation, G15S, which stabilises F-actin, as do the activating actins S14C and V159N. The three mutants share several biochemical properties, but can be distinguished by their ability to bind cofilin, ATP and MAL. MAL interaction with actin S14C is essentially undetectable, and that with actin V159N is weakened. In contrast, actin G15S interacts more strongly with MAL than the wild-type protein. Strikingly, the nuclear accumulation of MAL induced by overexpression of actin S14C is substantially dependent on Rho activity and actin treadmilling, while that induced by actin G15S expression is not. We propose a model in which actin G15S acts directly to promote MAL nuclear entry.

Item Type: Article
Additional Information: PMCID: PMC524340
Keywords: Actin Depolymerizing Factors, Actins, Active Transport, Cell Nucleus, Adenosine Triphosphate, Amino Acid Motifs, Amino Acid Sequence, Animals, Binding Sites, Cell Extracts, Cell Nucleus, DNA-Binding Proteins, Deoxyribonuclease I, Genes, Reporter, Glutathione Transferase, Luciferases, Mice, Microfilament Proteins, NIH 3T3 Cells, Oncogene Proteins, Fusion, Phalloidine, Point Mutation, Precipitin Tests, Protein Binding, Serum Response Factor, Signal Transduction, Two-Hybrid System Techniques
SGUL Research Institute / Research Centre: Academic Structure > Institute of Medical & Biomedical Education (IMBE)
Academic Structure > Institute of Medical & Biomedical Education (IMBE) > Centre for Biomedical Education (INMEBE)
Journal or Publication Title: EMBO J
ISSN: 0261-4189
Dates:
DateEvent
13 October 2004Published
PubMed ID: 15385960
Web of Science ID: 15385960
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URI: http://openaccess.sgul.ac.uk/id/eprint/2067
Publisher's version: https://doi.org/10.1038/sj.emboj.7600404

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