Godoi, Paulo H. C. and Wilkie-Grantham, Rachel P. and Hishiki, Asami and Sano, Renata and Matsuzawa, Yasuko and Yanagi, Hiroko and Munte, Claudia E. and Chen, Ya and Yao, Yong and Marassi, Francesca M. and Kalbitzer, Hans R. and Matsuzawa, Shu-ichi and Reed, John C. (2016) Orphan Nuclear Receptor NR4A1 Binds a Novel Protein Interaction Site on Anti-apoptotic B Cell Lymphoma Gene 2 Family Proteins. JOURNAL OF BIOLOGICAL CHEMISTRY, 291 (27). pp. 14072-14084. ISSN 0021-9258, 1083-351X
Full text not available from this repository. (Request a copy)Abstract
B cell lymphoma gene 2 (Bcl-2) family proteins are key regulators of programmed cell death and important targets for drug discovery. Pro-apoptotic and anti-apoptotic Bcl-2 family proteins reciprocally modulate their activities in large part through protein interactions involving a motif known as BH3 (Bcl-2 homology 3). Nur77 is an orphan member of the nuclear receptor family that lacks a BH3 domain but nevertheless binds certain anti-apoptotic Bcl-2 family proteins (Bcl-2, Bfl-1, and Bcl-B), modulating their effects on apoptosis and autophagy. We used a combination of NMR spectroscopy-based methods, mutagenesis, and functional studies to define the interaction site of a Nur77 peptide on anti-apoptotic Bcl-2 family proteins and reveal a novel interaction surface. Nur77 binds adjacent to the BH3 peptide-binding crevice, suggesting the possibility of cross-talk between these discrete binding sites. Mutagenesis of residues lining the identified interaction site on Bcl-B negated the interaction with Nur77 protein in cells and prevented Nur77-mediated modulation of apoptosis and autophagy. The findings establish a new protein interaction site with the potential to modulate the apoptosis and autophagy mechanisms governed by Bcl-2 family proteins.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | BH3 MIMETIC ABT-737; BCL-B; NMR-SPECTROSCOPY; RESISTANCE; AUTOPHAGY; NUR77; BFL-1; CONFORMATION; INHIBITORS; CONVERSION; apoptosis; autophagy; B cell lymphoma 2 (Bcl-2) family; NMR; protein-protein interaction; Bcl-b; Bfl-1; NR4A1; Nur77 |
| Subjects: | 500 Science > 570 Life sciences |
| Divisions: | Biology, Preclinical Medicine > Institut für Biophysik und physikalische Biochemie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 09 Apr 2019 11:35 |
| Last Modified: | 09 Apr 2019 11:35 |
| URI: | https://pred.uni-regensburg.de/id/eprint/3672 |
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