The DOI matches its Crossref record; 8 of the 8 references it cites were found in a registry or an index.
PUMA binding induces partial unfolding within BCL-xL to disrupt p53 binding and promote apoptosis
Open accessAbstract
Following DNA damage, nuclear p53 induces the expression of PUMA, a BH3-only protein that binds and inhibits the anti-apoptotic BCL-2 repertoire, including BCL-xL. PUMA, unique amongst BH3-only proteins, disrupts the interaction between cytosolic p53 and BCL-xL, allowing p53 to promote apoptosis via direct activation of the BCL-2 effector molecules, BAX and BAK. Structural investigations using nuclear magnetic resonance spectroscopy and X-ray crystallography revealed that PUMA binding induced partial unfolding of two α-helices within BCL-xL. Wild-type PUMA or a PUMA mutant incapable of causing binding-induced unfolding of BCL-xL equivalently inhibited the anti-apoptotic BCL-2 repertoire to sensitize for death receptor (DR)-activated apoptosis, but only wild-type PUMA promoted p53-dependent, DNA damage-induced apoptosis. Our data suggest that PUMA-induced partial unfolding of BCL-xL disrupts interactions between cytosolic p53 and BCL-xL, releasing the bound p53 to initiate apoptosis. We propose that regulated unfolding of BCL-xL provides a mechanism to promote PUMA-dependent signaling within the apoptotic pathways.
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Cites
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“In contrast, PUMA, PUMA BH3 , PUMA BH3 W → A , PUMA-BAD BH3 and BAD BH3 were all active in derepressing a complex of BCL-xL and C8-BID to promote BAX activation and MOMP (Supplementary Fig.”
InfluentialSelf-citationChen, L., Willis, S. N., Wei, A., Smith, B. J., Fletcher, J. I., Hinds, M. G., Colman, P. M., Day, C. L., Adams, J. M., & Huang, D. C. S. (2005) · Molecular Cell · doi:10.1016/j.molcel.2004.12.030 · Cited by 1,816
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Many players in BCL-2 family affairs
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Self-citationPhysiological and Pharmacological Control of BAK, BAX, and Beyond
Luna-Vargas, M. P. A., & Chipuk, J. E. (2016) · Trends in Cell Biology · doi:10.1016/j.tcb.2016.07.002 · Cited by 142
Self-citationAllosteric inhibition of antiapoptotic MCL-1
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Metadata
- Authors
- Follis, A. V., Chipuk, J. E., Fisher, J. C., Yun, M.-K., Grace, C. R., Nourse, A., Baran, K., Ou, L., Min, L., White, S. W., Green, D. R., & Kriwacki, R. W.
- Venue
- Nature Chemical Biology
- Published
- 2013-01-20
- Volume
- 9
- Issue
- 3
- Pages
- 163-168
- ISSN
- 1552-4450 (ISSN-L)
- 1552-4469
- OpenAlex
- W1974349185
- Cited by
- 174
- References
- 8
- FWCI
- 8.74
- Type
- journal article
- Language
- en
- Open access
- green
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- Follis, A. V., Chipuk, J. E., Fisher, J. C., Yun, M.-K., Grace, C. R., Nourse, A., Baran, K., Ou, L., Min, L., White, S. W., Green, D. R., & Kriwacki, R. W. (2013). PUMA binding induces partial unfolding within BCL-xL to disrupt p53 binding and promote apoptosis. Nature Chemical Biology. https://doi.org/10.1038/nchembio.1166
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