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Updated: Jun 15, 2026

Induction and Analysis of Epithelial to Mesenchymal Transition
Published on: August 27, 2013
Epithelial Protein Lost in Neoplasm alpha (Eplin-alpha) is transcriptionally regulated by G-actin and MAL/MRTF
Laura Leitner1, Dmitry Shaposhnikov, Arnaud Descot
1AG Regulation of Gene Expression, Department of Molecular Biology, Max-Planck-Institute of Biochemistry, D-82152 Martinsried, Germany.
Abstract:
Epithelial Protein Lost in Neoplasm alpha is a novel cytoskeleton-associated tumor suppressor whose expression inversely correlates with cell growth, motility, invasion and cancer mortality. Here we show that Eplin-alpha transcription is regulated by actin-MAL-SRF signalling. Upon signal induction, the coactivator MAL/MRTF is released from a repressive complex with monomeric actin, binds the transcription factor SRF and activates target gene expression. In a transcriptome analysis with a combination of actin binding drugs which specifically and differentially interfere with the actin-MAL complex (Descot et al., 2009), we identified Eplin to be primarily controlled by monomeric actin. Further analysis revealed that induction of the Eplin-alpha mRNA and its promoter was sensitive to drugs and mutant actins which stabilise the repressive actin-MAL complex. In contrast, the Eplin-beta isoform remained unaffected. Knockdown of MRTFs or dominant negative MAL which inhibits SRF-mediated transcription impaired Eplin-alpha expression. Conversely, constitutively active mutant actins and MAL induced Eplin-alpha. MAL and SRF were bound to a consensus SRF binding site of the Eplin-alpha promoter; the recruitment of MAL to this region was enhanced severalfold upon induction. The tumor suppressor Eplin-alpha is thus a novel cytoskeletal target gene transcriptionally regulated by the actin-MAL-SRF pathway, which supports a role in cancer biology.
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