Besides its well-characterized function as a cytoskeletal component, actin has emerged as a regulator of nuclear processes, including transcription. MAL, a coactivator of the transcription factor serum response factor (SRF), directly binds to and senses cellular levels of monomeric actin (G-actin). MAL responds to serum-induced depletion of cellular G-actin with nuclear accumulation and SRF activation. Vartiainen et al. (see the Perspective by Wu and Crabtree) report that MAL rapidly shuttles between the nucleus and the cytoplasm in resting cells. Actin binding in the nucleus targets MAL for efficient nuclear export and, furthermore, prevents activation of SRF during the short time that MAL spends in the nucleus. When growth factor stimulation interferes with actin binding, this lock on MAL activity is released.
M. K. Vartiainen, S. Guettler, B. Larijani, R. Treisman, Nuclear actin regulates dynamic subcellular localization and activity of the SRF cofactor MAL. Science 316, 1749-1752 (2007). [Abstract] [Full Text]