Negative Regulation of the EGFR-MAPK Cascade by Actin-MAL-Mediated Mig6/Errfi-1 Induction
作者： Arnaud Descot , Reinhard Hoffmann , Dmitry Shaposhnikov , Markus Reschke , Axel Ullrich
DOI: 10.1016/J.MOLCEL.2009.07.015
关键词: MAPK cascade 、 Cancer research 、 Regulation of gene expression 、 MAPK/ERK pathway 、 Gene expression 、 Biology 、 Transactivation 、 Signal transduction 、 Serum response factor 、 Downregulation and upregulation 、 Cell biology 、 Molecular biology
摘要: We analyzed the G-actin-regulated transcriptome by gene expression analysis using previously characterized actin-binding drugs. found many known MAL/MRTF-dependent target genes of serum response factor (SRF), as well additional directly regulated genes. Surprisingly, several putative antiproliferative were identified, including mig6/errfi-1, a negative regulator EGFR family. Mig6 induction occurred through actin-MAL-SRF signaling, and MAL was inducibly recruited to activated mig6 promoter element. Upregulation lipid agonists such LPA S1P or actin drugs involved correlated with decreased activation EGFR, MAPK/Erk, c-fos. depletion restored signaling provided proliferative advantage. Overexpression exhibited strong effects requiring domains for SRF binding transactivation, which supports antagonistic functions on growth-promoting signals. Our results show existence negatively acting transcriptional networks between pro- pathways toward SRF.
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