Article
- The EMBO Journal (2004) 23, 3973 - 3983
- doi:10.1038/sj.emboj.7600404
Published online: 23 September 2004
Subject Categories:
Mutant actins that stabilise F-actin use distinct mechanisms to activate the SRF coactivator MAL
Guido Poserna, Francesc Miralles, Sebastian Guettler and Richard Treisman
- Transcription Laboratory, Cancer Research UK London Research Institute, Lincoln's Inn Fields Laboratories, London, UK
Correspondence to:
Richard Treisman, Transcription Laboratory, Room 401, Cancer Research UK, PO Box 123, 44 Lincoln's Inn Fields, London WC2A 3PX, UK. Tel.: +44 207 269 3271; Fax: +44 207 269 3093; E-mail: richard.treisman@cancer.org.uk
aPresent address: Max-Planck-Institute of Biochemistry, Am Klopferspitz 18, 82152 Martinsried, Germany
Received 10 May 2004; Accepted 19 August 2004
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.
Keywords:
- actin,
- MAL,
- MKL1,
- Rho,
- SRF
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