Actin dynamics control SRF activity by regulation of its coactivator MAL
Open accessAbstract
Rho GTPases regulate the transcription factor SRF via their ability to induce actin polymerization. SRF activity responds to G actin, but the mechanism of this has remained unclear. We show that Rho-actin signaling regulates the subcellular localization of the myocardin-related SRF coactivator MAL, rearranged in t(1;22)(p13;q13) AML. The MAL-SRF interaction displays the predicted properties of a Rho-regulated SRF cofactor. MAL is predominantly cytoplasmic in serum-starved cells, but accumulates in the nucleus following serum stimulation. Activation of the Rho-actin signaling pathway is necessary and sufficient to promote MAL nuclear accumulation. MAL N-terminal sequences, including two RPEL motifs, are required for the response to signaling, while other regions mediate its nuclear export (or cytoplasmic retention) and nuclear import. MAL associates with unpolymerized actin through its RPEL motifs. Constitutively cytoplasmic MAL derivatives interfere with MAL redistribution and Rho-actin signaling to SRF. MAL associates with several SRF target promoters regulated via the Rho-actin pathway.
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RhoA-mediated actin polymerization through ROCK/LIMK or mDia reduces the interaction between actin and MKL-1, inhibiting the actin-dependent nuclear export of MKL-1, which results in its nuclear accumulation and enhanced SRF-mediated transcription.
“RhoA-mediated actin polymerization through ROCK/LIMK or mDia reduces the interaction between actin and MLK-1, thus inhibiting the actin-dependent nuclear export of MKL-1, which results in its nuclear accumulation and enhanced SRF-mediated transcription [167].”
From RhoA Signaling in Neurodegenerative Diseases (2022) · cites this paper as [167]
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- Authors
- Miralles, F., Posern, G., Zaromytidou, A.-I., & Treisman, R.
- Affiliations
- Cancer Research UK (GB)
- Corresponding author
- Treisman, Richard
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2003-05
- Volume
- 113
- Issue
- 3
- Pages
- 329-342
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W2093723806
- Cited by
- 1,327
- References
- 1
- Citations by year
- 2026: 46 · 2025: 34 · 2024: 43 · 2023: 43 · 2022: 64 · 2021: 52 · 2020: 61 · 2019: 68 · 2018: 70 · 2017: 59 · 2016: 68 · 2015: 70 · 2014: 71 · 2013: 65 · 2012: 62
- FWCI
- 17.80
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Keywords
- SRF, Rho GTPases, actin polymerization, nuclear localization, transcriptional coactivator, serum stimulation, nuclear import, cytoplasmic retention
- MeSH terms
- Actins, Amino Acid Sequence, Animals, Binding Sites, Cell Line, Cell Nucleus, DNA, DNA-Binding Proteins, Humans, Molecular Sequence Data, Phosphorylation, Signal Transduction, Oncogene Proteins, Fusion, Trans-Activators, 3T3 Cells, Conserved Sequence, rho GTP-Binding Proteins, Amino Acid Motifs, Active Transport, Cell Nucleus, Electrophoretic Mobility Shift Assay, Serum Response Factor, Macromolecular Substances, Mice
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