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| Identification of small-molecule inhibitors of interaction between the BH3 domain and Bcl-x(L) |
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| Author(s): Degterev A, Lugovskoy A, Cardone M, Mulley B, Wagner G, Mitchison T, Yuan JY |
| Source: NATURE CELL BIOLOGY Volume: 3 Issue: 2 Pages: 173-182 Published: FEB 2001 |
| Times Cited: 305 References: 49 |
| Abstract: To study the role of the BH3 domain in mediating pro-apoptotic and anti-apoptotic activities of Bcl-2 family members, we identified a series of novel small molecules (BH3Is) that inhibit the binding of the Bak BH3 peptide to Bcl-x(L). NMR analyses revealed that BH3Is target the BH3-binding pocket of Bcl-x(L). Inhibitors specifically block the BH3-domain-mediated heterodimerization between Bcl-2 family members in vitro and in vivo and induce apoptosis. Our results indicate that BH3-dependent heterodimerization is the key function of anti-apoptotic Bcl-2 family members and is required for the maintenance of cellular homeostasis. |
| Document Type: Article |
| Language: English |
| Reprint Address: Yuan, JY (reprint author), Harvard Univ, Sch Med, Dept Cell Biol, 240 Longwood Ave, Boston, MA 02115 USA |
Addresses:
1. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA
2. Harvard Univ, Sch Med, Inst Chem & Cell Biol, Boston, MA 02115 USA
3. Harvard Univ, Comm Higher Degrees Biophys, Cambridge, MA 02138 USA
4. Harvard Univ, Sch Med, Dept Mol Pharmacol & Biochem, Boston, MA 02115 USA
5. MIT, Dept Biol, Cambridge, MA 02138 USA |
| Publisher: MACMILLAN PUBLISHERS LTD, PORTERS SOUTH, 4 CRINAN ST, LONDON N1 9XW, ENGLAND |
| Subject Category: Cell Biology |
| IDS Number: 399CG |
| ISSN: 1465-7392 |
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| | | | | | | | | Record from Web of Science® | | | | | | | | | |