Ayer, D E and Lawrence, Q A and Eisenman, R N (1995) Mad-Max transcriptional repression is mediated by ternary complex formation with mammalian homologs of yeast repressor Sin3. Cell, 80 (5). pp. 767-776. ISSN 0092-8674
Abstract
The bHLH-ZIP protein Mad heterodimerizes with Max as a sequence-specific transcriptional repressor. Mad is rapidly induced upon differentiation, and the associated switch from Myc-Max to Mad-Max heterocomplexes seem to repress genes normally activated by Myc-Max. We have identified two related mammalian cDNAs that encode Mad-binding proteins. Both possess sequence homology with the yeast transcription repressor Sin3, including four conserved paired amphipathic helix (PAH) domains. mSin3A and mSin3B bind specifically to Mad and the related protein Mxi1. Mad-Max and mSin3 form ternary complexes in solution that specifically recognize the Mad-Max E box-binding site. Mad-mSin3 association requires PAH2 of mSin3A/mSin3B and the first 25 residues of Mad, which contains a putative amphipathic alpha-helical region. Point mutations in this region eliminate interaction with mSin3 proteins and block Mad transcriptional repression. We suggest that Mad-Max represses transcription by tethering mSin3 to DNA as corepressors and that a transcriptional repression mechanism is conserved from yeast to mammals.
| Item Type: | Article or Abstract |
|---|---|
| Additional Information: | This article is freely available at the journal's website. |
| DOI: | 10.1016/0092-8674(95)90355-0 |
| PubMed ID: | 7889570 |
| Grant Numbers: | RO1 CA57138 |
| Keywords or MeSH Headings: | Amino Acid Sequence; Amino Acids/analysis; Animals; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; Basic-Leucine Zipper Transcription Factors; Cell Line; Cloning, Molecular; DNA-Binding Proteins/genetics/metabolism; Fungal Proteins/metabolism; Kidney/embryology; Mice; Molecular Sequence Data; Repressor Proteins/genetics/metabolism; Saccharomyces cerevisiae/chemistry; Saccharomyces cerevisiae Proteins; Sequence Alignment; Sequence Analysis, DNA; Sequence Deletion/physiology; Sequence Homology, Amino Acid; Stem Cells; Transcription Factors; Transcription, Genetic/physiology; |
| Subjects: | Molecules > Proteins > Transcription factors Molecules > Molecular structure Cellular and Organismal Processes > Genetic processes > Transcription |
| Depositing User: | Library Staff |
| Date Deposited: | 26 Nov 2008 21:45 |
| Last Modified: | 07 May 2010 20:29 |
| URI: | http://authors.fhcrc.org/id/eprint/153 |
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