The DOI matches its Crossref record; 36 of the 36 references it cites were found in a registry or an index.
The Heat Shock Protein 90 Antagonist Novobiocin Interacts with a Previously Unrecognized ATP-binding Domain in the Carboxyl Terminus of the Chaperone
Open accessAbstract
Heat shock protein 90 (Hsp90), one of the most abundant chaperones in eukaryotes, participates in folding and stabilization of signal-transducing molecules including steroid hormone receptors and protein kinases. The amino terminus of Hsp90 contains a non-conventional nucleotide-binding site, related to the ATP-binding motif of bacterial DNA gyrase. The anti-tumor agents geldanamycin and radicicol bind specifically at this site and induce destabilization of Hsp90-dependent client proteins. We recently demonstrated that the gyrase inhibitor novobiocin also interacts with Hsp90, altering the affinity of the chaperone for geldanamycin and radicicol and causing in vitro and in vivo depletion of key regulatory Hsp90-dependent kinases including v-Src, Raf-1, and p185(ErbB2). In the present study we used deletion/mutation analysis to identify the site of interaction of novobiocin with Hsp90, and we demonstrate that the novobiocin-binding site resides in the carboxyl terminus of the chaperone. Surprisingly, this motif also recognizes ATP, and ATP and novobiocin efficiently compete with each other for binding to this region of Hsp90. Novobiocin interferes with association of the co-chaperones Hsc70 and p23 with Hsp90. These results identify a second site on Hsp90 where the binding of small molecule inhibitors can significantly impact the function of this chaperone, and they support the hypothesis that both amino- and carboxyl-terminal domains of Hsp90 interact to modulate chaperone activity.
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Cites
Steroid Receptor Interactions with Heat Shock Protein and Immunophilin Chaperones*
Pratt, W. B., & Toft, D. O. (1997) · Endocrine Reviews · doi:10.1210/edrv.18.3.0303 · Cited by 1,791
Stebbins, C. E., Russo, A. A., Schneider, C., Rosen, N., Hartl, F. U., & Pavletich, N. P. (1997) · Cell · doi:10.1016/s0092-8674(00)80203-2 · Cited by 1,364
Prodromou, C., Roe, S. M., O'Brien, R., Ladbury, J. E., Piper, P. W., & Pearl, L. H. (1997) · Cell · doi:10.1016/s0092-8674(00)80314-1 · Cited by 1,265
The biology of heat shock proteins and molecular chaperones
Buchner, J. (1994) · Trends in Biochemical Sciences · doi:10.1016/0968-0004(94)90065-5 · Cited by 1,205
Roe, S. M., Prodromou, C., O'Brien, R., Ladbury, J. E., Piper, P. W., & Pearl, L. H. (1999) · Journal of Medicinal Chemistry · doi:10.1021/jm980403y · Cited by 1,004
Grenert, J. P., Sullivan, W. P., Fadden, P., Haystead, T. A. J., Clark, J., Mimnaugh, E., Krutzsch, H., Ochel, H.-J., Schulte, T. W., Sausville, E., et al. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.38.23843 · Cited by 569
Self-citationMammalian p50Cdc37 is a protein kinase-targeting subunit of Hsp90 that binds and stabilizes Cdk4
Stepanova, L., Leng, X., Parker, S. B., & Harper, J. W. (1996) · Genes & Development · doi:10.1101/gad.10.12.1491 · Cited by 483
Regulation of Hsp90 ATPase activity by tetratricopeptide repeat (TPR)-domain co-chaperones
Prodromou, C. (1999) · The EMBO Journal · doi:10.1093/emboj/18.3.754 · Cited by 425
Novobiocin and Related Coumarins and Depletion of Heat Shock Protein 90-Dependent Signaling Proteins
Marcu, M. G., Schulte, T. W., & Neckers, L. (2000) · JNCI: Journal of the National Cancer Institute · doi:10.1093/jnci/92.3.242 · Cited by 405
Self-citationMutant conformation of p53 translated in vitro or in vivo requires functional HSP90.
Blagosklonny, M. V., Toretsky, J., Bohen, S., & Neckers, L. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.16.8379 · Cited by 314
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Cited by
HSP90 and the chaperoning of cancer
Whitesell, L., & Lindquist, S. L. (2005) · Nature Reviews Cancer · doi:10.1038/nrc1716 · Cited by 2,502
Schopf, F. H., Biebl, M. M., & Buchner, J. (2017) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm.2017.20 · Cited by 1,540
Coumarin-Based Small-Molecule Fluorescent Chemosensors
Cao, D., Liu, Z., Verwilst, P., Koo, S., Jangjili, P., Kim, J. S., & Lin, W. (2019) · Chemical Reviews · doi:10.1021/acs.chemrev.9b00145 · Cited by 1,306
Hsp90 Molecular Chaperone Inhibitors: Are We There Yet?
Neckers, L., & Workman, P. (2012) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-11-1000 · Cited by 891
Self-citationHeat Shock Proteins and Cancer
Wu, J., Liu, T., Rios, Z., Mei, Q., Lin, X., & Cao, S. (2017) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2016.11.009 · Cited by 696
Metadata
- Authors
- Marcu, M. G., Chadli, A., Bouhouche, I., Catelli, M., & Neckers, L. M.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2000-11
- Volume
- 275
- Issue
- 47
- Pages
- 37181-37186
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2054290614
- Cited by
- 502
- References
- 36
- FWCI
- 4.84
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Marcu, M. G., Chadli, A., Bouhouche, I., Catelli, M., & Neckers, L. M. (2000). The Heat Shock Protein 90 Antagonist Novobiocin Interacts with a Previously Unrecognized ATP-binding Domain in the Carboxyl Terminus of the Chaperone. Journal of Biological Chemistry. https://doi.org/10.1074/jbc.m003701200
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