| | |  | | | | Record from Web of Science® | | | | | | |
| Mad proteins contain a dominant transcription repression domain |
|
|
| Author(s): Ayer DE, Laherty CD, Lawrence QA, Armstrong AP, Eisenman RN |
| Source: MOLECULAR AND CELLULAR BIOLOGY Volume: 16 Issue: 10 Pages: 5772-5781 Published: OCT 1996 |
| Times Cited: 114 References: 80 |
| Abstract: Transcription repression by the basic region-helix-loop-helix-zipper (bHLHZip) protein Mad1 requires DNA binding as a ternary complex with Max and mSinSA or mSin3B, the mammalian orthologs of the Saccharomyces cerevisiae transcriptional corepressor SIN3. The interaction between Mad1 and mSin3 is mediated by three potential amphipathic alpha-helices: one in the N terminus of Mad (mSin interaction domain, or SID) and two within the second pail ed amphipathic helix domain (PAH2) of mSin3A. Mutations that alter the structure of the SID inhibit in vitro interaction between Mad and mSin3 and inactivate Mad's transcriptional repression activity, sere me show that a 35-residue region containing the SID represents a dominant repression domain whose activity can be transferred to a heterologous DNA binding region. A fusion protein comprising the Mad1 SID linked to a Gal4 DNA binding domain mediates repression of minimal as well as complex promoters dependent on Gal4 DNA binding sites, Ln addition, the SID represses the transcriptional activity of linked VP16 and c-Myc transactivation domains. When fused to a full-length c-Myc protein, the Mad1 SID specifically represses both c-Myc's transcriptional and transforming activities. Fusions between the GAL DNA binding domain and full-length mSin3 mere also capable of repression. We show that the association between Mad1 and mSin3 is not only dependent on the helical SID but is also dependent on both putative helices of the mSin3 PAH2 region, suggesting that stable interaction requires all three helices, Our results indicate that the SID is necessary and sufficient for transcriptional repression mediated by the Mad protein family and that SID repression is dominant over several distinct transcriptional activators. |
| Document Type: Article |
| Language: English |
Addresses:
1. FRED HUTCHINSON CANC RES CTR, DIV BASIC SCI, SEATTLE, WA 98014 USA
2. FRED HUTCHINSON CANC RES CTR, PROGRAM MOL & CELLULAR BIOL, SEATTLE, WA 98014 USA |
| Publisher: AMER SOC MICROBIOLOGY, 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 |
| Subject Category: Biochemistry & Molecular Biology; Cell Biology |
| IDS Number: VH852 |
| ISSN: 0270-7306 |
|
| | | | | | | | | Record from Web of Science® | | | | | | | | | |