|
 |
|
|
| Subject Categories: Signal Transduction | Chromatin & Transcription |
|
| The EMBO Journal
(2004) 23, 3973–3983, doi:10.1038/sj.emboj.7600404 Published online 23 September 2004 |
|
| Mutant actins that stabilise F-actin use distinct mechanisms to activate the SRF coactivator MAL |
|
|
| Guido Posern1, Francesc Miralles, Sebastian Guettler and Richard Treisman |
|
|
Transcription Laboratory, Cancer Research UK London Research Institute, Lincoln's Inn Fields Laboratories, London, UK To whom correspondence should be addressed 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 1 Present address: Max-Planck-Institute of Biochemistry, Am Klopferspitz 18, 82152 Martinsried, Germany Received 10 May 2004; Accepted 19 August 2004; Published online 23 September 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 |
|
|
|
Top of page MORE ARTICLES LIKE THISThese links to content published by NPG are automatically generated NEWS AND VIEWSSCAI blocks MAL-evolent effects on cancer cell invasion Nature Cell Biology News and Views (01 May 2009) Nature Structural Biology News and Views (01 Sep 2001) RESEARCHCerebral blood flow response in adenosine 2a receptor knockout mice during transient hypoxic hypoxia Journal of Cerebral Blood Flow & Metabolism Original Article Journal of Cerebral Blood Flow & Metabolism Original Article |
|
|
| |
| |
| |
 | Email link to a friend |
| |
 | Download PDF |
| |
 | Full text |
| |
| |
| |
 | Next article |
| |
 | Previous article |
| |
 | Table of contents |
| |
| |
 | Rights and permissions |
| |
 | Reprints |
| |
| |
| |
 Register for table of contents by email | |
| |
| |
| |
