File Download
Links for fulltext
(May Require Subscription)
- Publisher Website: 10.1039/C5SC00633C
- Scopus: eid_2-s2.0-84935851693
- PMID: 28717468
- WOS: WOS:000356176200058
- Find via
Supplementary
- Citations:
- Appears in Collections:
Article: Natural products triptolide, celastrol, and withaferin A inhibit the chaperone activity of peroxiredoxin I
Title | Natural products triptolide, celastrol, and withaferin A inhibit the chaperone activity of peroxiredoxin I |
---|---|
Authors | |
Issue Date | 2015 |
Citation | Chemical Science, 2015, v. 6 n. 7, p. 4124-4130 How to Cite? |
Abstract | Peroxiredoxin I (Prx I) plays an important role in cancer development and inflammation. It is a dual-functional protein which acts as both an antioxidant enzyme and a molecular chaperone. While there have been intensive studies on its peroxidase activity, Prx I's chaperone activity remains elusive, likely due to the lack of chaperone inhibitors. Here we report that natural product triptolide selectively inhibits the chaperone activity of Prx I, but not its peroxidase activity. Through direct interaction with corresponding cysteines, triptolide triggers dissociation of high-molecular-weight oligomers of Prx I, and thereby inhibits its chaperone activity in a dose-dependent manner. We have also identified celastrol and withaferin A as novel Prx I chaperone inhibitors that are even more potent than triptolide in the chaperone activity assay. By revealing the exact molecular mechanisms of interaction and inhibition, the current study provides the first Prx I chaperone inhibitors as promising pharmacological tools for modulating and dissecting the chaperone function of Prx I. |
Persistent Identifier | http://hdl.handle.net/10722/220597 |
ISSN | 2023 Impact Factor: 7.6 2023 SCImago Journal Rankings: 2.333 |
PubMed Central ID | |
ISI Accession Number ID |
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Zhao, Q | - |
dc.contributor.author | Ding, Y | - |
dc.contributor.author | Deng, ZS | - |
dc.contributor.author | Lee, OY | - |
dc.contributor.author | Gao, P | - |
dc.contributor.author | Chen, P | - |
dc.contributor.author | Rose, RJ | - |
dc.contributor.author | Zhao, H | - |
dc.contributor.author | Zhang, ZF | - |
dc.contributor.author | Tao, X | - |
dc.contributor.author | Heck, AJR | - |
dc.contributor.author | Kao, RYT | - |
dc.contributor.author | Yang, D | - |
dc.date.accessioned | 2015-10-16T06:46:43Z | - |
dc.date.available | 2015-10-16T06:46:43Z | - |
dc.date.issued | 2015 | - |
dc.identifier.citation | Chemical Science, 2015, v. 6 n. 7, p. 4124-4130 | - |
dc.identifier.issn | 2041-6520 | - |
dc.identifier.uri | http://hdl.handle.net/10722/220597 | - |
dc.description.abstract | Peroxiredoxin I (Prx I) plays an important role in cancer development and inflammation. It is a dual-functional protein which acts as both an antioxidant enzyme and a molecular chaperone. While there have been intensive studies on its peroxidase activity, Prx I's chaperone activity remains elusive, likely due to the lack of chaperone inhibitors. Here we report that natural product triptolide selectively inhibits the chaperone activity of Prx I, but not its peroxidase activity. Through direct interaction with corresponding cysteines, triptolide triggers dissociation of high-molecular-weight oligomers of Prx I, and thereby inhibits its chaperone activity in a dose-dependent manner. We have also identified celastrol and withaferin A as novel Prx I chaperone inhibitors that are even more potent than triptolide in the chaperone activity assay. By revealing the exact molecular mechanisms of interaction and inhibition, the current study provides the first Prx I chaperone inhibitors as promising pharmacological tools for modulating and dissecting the chaperone function of Prx I. | - |
dc.language | eng | - |
dc.relation.ispartof | Chemical Science | - |
dc.rights | This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License. | - |
dc.title | Natural products triptolide, celastrol, and withaferin A inhibit the chaperone activity of peroxiredoxin I | - |
dc.type | Article | - |
dc.identifier.email | Lee, OY: leeonyi@hku.hk | - |
dc.identifier.email | Chen, P: chenpin@hku.hk | - |
dc.identifier.email | Kao, RYT: rytkao@hkucc.hku.hk | - |
dc.identifier.email | Yang, D: yangdan@hku.hk | - |
dc.identifier.authority | Lee, OY=rp00725 | - |
dc.identifier.authority | Kao, RYT=rp00481 | - |
dc.identifier.authority | Yang, D=rp00825 | - |
dc.description.nature | published_or_final_version | - |
dc.identifier.doi | 10.1039/C5SC00633C | - |
dc.identifier.pmid | 28717468 | - |
dc.identifier.pmcid | PMC5497274 | - |
dc.identifier.scopus | eid_2-s2.0-84935851693 | - |
dc.identifier.hkuros | 255394 | - |
dc.identifier.volume | 6 | - |
dc.identifier.issue | 7 | - |
dc.identifier.spage | 4124 | - |
dc.identifier.epage | 4130 | - |
dc.identifier.eissn | 2041-6539 | - |
dc.identifier.isi | WOS:000356176200058 | - |
dc.identifier.issnl | 2041-6520 | - |