Epithelial Protein Lost in Neoplasm α (Eplin-α) is transcriptionally regulated by G-actin and MAL/MRTF coactivators

Molecular Cancer

Short Communication

Dmitry Shaposhnikov¹  Guido Posern¹  Arnaud Descot¹  Laura Leitner¹  Reinhard Hoffmann² 

[1] AG Regulation of Gene Expression, Department of Molecular Biology, Max-Planck-Institute of Biochemistry, D-82152, Martinsried, Germany;Institute of Medical Microbiology and Immunology, Technical University of Munich, D-81675, München, Germany;

关键词: Cytochalasin;    Serum Response Factor;    Mouse Mammary Epithelial Cell;    Serum Induction;    Jasplakinolide;   

DOI  :  10.1186/1476-4598-9-60

 received in 2009-12-03, accepted in 2010-03-17,  发布年份 2010

来源: Springer

【 摘 要 】

Epithelial Protein Lost in Neoplasm α is a novel cytoskeleton-associated tumor suppressor whose expression inversely correlates with cell growth, motility, invasion and cancer mortality. Here we show that Eplin-α 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-α mRNA and its promoter was sensitive to drugs and mutant actins which stabilise the repressive actin-MAL complex. In contrast, the Eplin-β isoform remained unaffected. Knockdown of MRTFs or dominant negative MAL which inhibits SRF-mediated transcription impaired Eplin-α expression. Conversely, constitutively active mutant actins and MAL induced Eplin-α. MAL and SRF were bound to a consensus SRF binding site of the Eplin-α promoter; the recruitment of MAL to this region was enhanced severalfold upon induction. The tumor suppressor Eplin-α is thus a novel cytoskeletal target gene transcriptionally regulated by the actin-MAL-SRF pathway, which supports a role in cancer biology.

【 授权许可】

Unknown   
© Leitner et al; licensee BioMed Central Ltd. 2010. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.