Mad upregulation and Id2 repression accompany transforming growth factor (TGF)-β-mediated epithelial cell growth suppression Journal Article
| Authors: | Siegel, P. M.; Shu, W.; Massagué, J. |
| Article Title: | Mad upregulation and Id2 repression accompany transforming growth factor (TGF)-β-mediated epithelial cell growth suppression |
| Abstract: | The growth inhibitory cytokine TGF-β enforces homeostasis of epithelia by activating processes such as cell cycle arrest and apoptosis. Id2 expression is often highest in proliferating epithelial cells and declines during differentiation. Recently, Id2 expression has been found to depend on Myc-Max transcriptional complexes. We observed that TGF-β signaling inhibits Id2 expression in human and mouse epithelial cell lines from different tissue origins. Furthermore, the observed Id2 down-regulation by TGF-β in mouse mammary epithelial cells occurs without a concurrent drop in c-Myc levels. However, sustained Id2 repression in these cells and in human keratinocytes coincides with induction of the Myc antagonistic repressors Mad2 and Mad4, decreased formation of Myc-Max heterodimers and the replacement of Myc-Max complexes with Mad-Max complexes on the Id2 promoter. These results argue that induction of Mad expression and Id2 down-regulation are important events during the TGF-β cytostatic program in epithelial cells. |
| Keywords: | controlled study; unclassified drug; human cell; dna-binding proteins; nonhuman; animal cell; mouse; animals; mice; cell cycle; cell division; complex formation; gene expression; cell growth; transforming growth factor beta; protein protein interaction; cell line; gene product; cell differentiation; transfection; keratinocyte; animalia; transcription factors; gene expression regulation; chromatin; nucleotide sequence; myc protein; genes, myc; recombinant proteins; breast epithelium; epithelium cell; epithelial cells; base sequence; gene control; dimerization; down regulation; upregulation; dna primers; inhibitor of differentiation 2; homeostasis; biochemistry; keratinocytes; repressor proteins; tissue; growth inhibition; cells; basic helix-loop-helix leucine zipper transcription factors; protein mad2; mitosis inhibition; cell cycles; helix-loop-helix motifs; inhibitor of differentiation protein 2; humans; human; priority journal; article; protein mad4 |
| Journal Title: | Journal of Biological Chemistry |
| Volume: | 278 |
| Issue: | 37 |
| ISSN: | 0021-9258 |
| Publisher: | American Society for Biochemistry and Molecular Biology |
| Date Published: | 2003-09-12 |
| Start Page: | 35444 |
| End Page: | 35450 |
| Language: | English |
| DOI: | 10.1074/jbc.M301413200 |
| PUBMED: | 12824180 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Export Date: 12 September 2014 -- Source: Scopus |
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