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Mutant actins that stabilise F‐actin use distinct mechanisms to activate the SRF coactivator MAL
Author(s) -
Posern Guido,
Miralles Francesc,
Guettler Sebastian,
Treisman Richard
Publication year - 2004
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/sj.emboj.7600404
Subject(s) - biology , actin , coactivator , cofilin , mutant , microbiology and biotechnology , serum response factor , actin remodeling , treadmilling , actin binding protein , mdia1 , microfilament , actin cytoskeleton , biochemistry , cytoskeleton , gene expression , transcription factor , cell , gene
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.