ArticleThe Journal of biological chemistry2018
X-linked inhibitor of apoptosis protein (XIAP) is a client of heat shock protein 70 (Hsp70) and a biomarker of its inhibition.
Article in The Journal of biological chemistry, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed.
- Regulation of translation elongation and integrated stress response in heat-shocked neurons.Cell reports · 2025Article
- Heat shock factor 1 is a promising therapeutic target against adult T-cell leukemia.Medical oncology (Northwood, London, England) · 2023Article
- MicroRNAs, long non-coding RNAs, and circular RNAs and gynecological cancers: focus on metastasis.Frontiers in oncology · 2023Review
- Alternative ATPase domain interactions in eukaryotic Hsp70 chaperones.Frontiers in molecular biosciences · 2023Review
- Role of methylation-related genesAnnals of translational medicine · 2022Article
- Heat shock proteins: Biological functions, pathological roles, and therapeutic opportunities.MedComm · 2022Review
- Multivalent protein-protein interactions are pivotal regulators of eukaryotic Hsp70 complexes.Cell stress & chaperones · 2022Review
- Review
- HSP70s in Breast Cancer: Promoters of Tumorigenesis and Potential Targets/Tools for Therapy.Cells · 2021Review
- HSP70 and FLT3-ITD: Targeting chaperone system to overcome drug resistance.Blood science (Baltimore, Md.) · 2021Article
- Unexpected specificity within dynamic transcriptional protein-protein complexes.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- The chaperone Hsp70 is a BH3 receptor activated by the pro-apoptotic Bim to stabilize anti-apoptotic clients.The Journal of biological chemistry · 2020Article
- Unravelling the Role of HSP70 as the Unexplored Molecular Target in Age-Related Macular Degeneration.Cureus · 2020Review
- 2-phenylethynesulfonamide inhibits growth of oral squamous cell carcinoma cells by blocking the function of heat shock protein 70.Bioscience reports · 2020Article
- Identification of hub genes associated with RNAi-induced silencing of XIAP through targeted proteomics approach in MCF7 cells.Cell & bioscience · 2020Article
- Targeting the interaction of AIMP2-DX2 with HSP70 suppresses cancer development.Nature chemical biology · 2020Article
- Hsp70 and Hsp40 inhibit an inter-domain interaction necessary for transcriptional activity in the androgen receptor.Nature communications · 2019Article
- 4-HNE Induces Apoptosis of Human Retinal Pigment Epithelial Cells by Modifying HSP70.Current medical science · 2019Article
- Novel insights into molecular chaperone regulation of ribonucleotide reductase.Current genetics · 2019Review
- MicroRNA‑186‑5p is expressed highly in ethanol‑induced cardiomyocytes and regulates apoptosis via the target gene XIAP.Molecular medicine reports · 2019Article
Corrections and comments
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Authors and funding
9 authors.
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Abstract
Heat shock protein 70 (Hsp70) and Hsp90 are molecular chaperones that play essential roles in tumor growth by stabilizing pro-survival client proteins. However, although the development of Hsp90 inhibitors has benefited from the identification of clients, such as Raf-1 proto-oncogene, Ser/Thr kinase (RAF1), that are particularly dependent on this chaperone, no equivalent clients for Hsp70 have been reported. Using chemical probes and MDA-MB-231 breast cancer cells, we found here that the inhibitors of apoptosis proteins, including c-IAP1 and X-linked inhibitor of apoptosis protein (XIAP), are obligate Hsp70 clients that are rapidly (within ∼3-12 h) lost after inhibition of Hsp70 but not of Hsp90. Mutagenesis and pulldown experiments revealed multiple Hsp70-binding sites on XIAP, suggesting that it is a direct, physical Hsp70 client. Interestingly, this interaction was unusually tight (∼260 nm) for an Hsp70-client interaction and involved non-canonical regions of the chaperone. Finally, we also found that Hsp70 inhibitor treatments caused loss of c-IAP1 and XIAP in multiple cancer cell lines and in tumor xenografts, but not in healthy cells. These results are expected to significantly accelerate Hsp70 drug discovery by providing XIAP as a pharmacodynamic biomarker. More broadly, our findings further suggest that Hsp70 and Hsp90 have partially non-overlapping sets of obligate protein clients in cancer cells.
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