HspBP1 is a dual function regulatory protein that controls both DNA repair and apoptosis in breast cancer cells
Abstract The Hsp70-binding protein 1 (HspBP1) belongs to a family of co-chaperones that regulate Hsp70 activity and whose biological significance is not well understood. In the present study, we show that when HspBP1 is either knocked down or overexpressed in BRCA1-proficient breast cancer cells, th...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Publishing Group
2022-04-01
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| Series: | Cell Death and Disease |
| Online Access: | https://doi.org/10.1038/s41419-022-04766-0 |
| _version_ | 1819061441363181568 |
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| author | Cha Kyung Youn Jung-Hee Lee Gurusamy Hariharasudhan Hong Beum Kim Jeeho Kim Sumi Lee Sung-Chul Lim Sang-Pil Yoon Sang-Gon Park In-Youb Chang Ho Jin You |
| author_facet | Cha Kyung Youn Jung-Hee Lee Gurusamy Hariharasudhan Hong Beum Kim Jeeho Kim Sumi Lee Sung-Chul Lim Sang-Pil Yoon Sang-Gon Park In-Youb Chang Ho Jin You |
| author_sort | Cha Kyung Youn |
| collection | DOAJ |
| description | Abstract The Hsp70-binding protein 1 (HspBP1) belongs to a family of co-chaperones that regulate Hsp70 activity and whose biological significance is not well understood. In the present study, we show that when HspBP1 is either knocked down or overexpressed in BRCA1-proficient breast cancer cells, there were profound changes in tumorigenesis, including anchorage-independent cell growth in vitro and in tumor formation in xenograft models. However, HspBP1 did not affect tumorigenic properties in BRCA1-deficient breast cancer cells. The mechanisms underlying HspBP1-induced tumor suppression were found to include interactions with BRCA1 and promotion of BRCA1-mediated homologous recombination DNA repair, suggesting that HspBP1 contributes to the suppression of breast cancer by regulating BRCA1 function and thereby maintaining genomic stability. Interestingly, independent of BRCA1 status, HspBP1 facilitates cell survival in response to ionizing radiation (IR) by interfering with the association of Hsp70 and apoptotic protease-activating factor-1. These findings suggest that decreased HspBP1 expression, a common occurrence in high-grade and metastatic breast cancers, leads to genomic instability and enables resistance to IR treatment. |
| first_indexed | 2024-12-21T14:42:56Z |
| format | Article |
| id | doaj.art-1f269d88fbf34ffb9aa56c3ce717f04d |
| institution | Directory Open Access Journal |
| issn | 2041-4889 |
| language | English |
| last_indexed | 2024-12-21T14:42:56Z |
| publishDate | 2022-04-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death and Disease |
| spelling | doaj.art-1f269d88fbf34ffb9aa56c3ce717f04d2022-12-21T19:00:07ZengNature Publishing GroupCell Death and Disease2041-48892022-04-0113411410.1038/s41419-022-04766-0HspBP1 is a dual function regulatory protein that controls both DNA repair and apoptosis in breast cancer cellsCha Kyung Youn0Jung-Hee Lee1Gurusamy Hariharasudhan2Hong Beum Kim3Jeeho Kim4Sumi Lee5Sung-Chul Lim6Sang-Pil Yoon7Sang-Gon Park8In-Youb Chang9Ho Jin You10DNA Damage Response Network Center, Chosun University School of MedicineDNA Damage Response Network Center, Chosun University School of MedicineDNA Damage Response Network Center, Chosun University School of MedicineDNA Damage Response Network Center, Chosun University School of MedicineDNA Damage Response Network Center, Chosun University School of MedicineDNA Damage Response Network Center, Chosun University School of MedicineDNA Damage Response Network Center, Chosun University School of MedicineDepartment of Anatomy, School of Medicine, Jeju National UniversityDepartment of Hemato-oncology, Chosun University Hospital Internal MedicineDepartment of Anatomy, Chosun University School of MedicineDNA Damage Response Network Center, Chosun University School of MedicineAbstract The Hsp70-binding protein 1 (HspBP1) belongs to a family of co-chaperones that regulate Hsp70 activity and whose biological significance is not well understood. In the present study, we show that when HspBP1 is either knocked down or overexpressed in BRCA1-proficient breast cancer cells, there were profound changes in tumorigenesis, including anchorage-independent cell growth in vitro and in tumor formation in xenograft models. However, HspBP1 did not affect tumorigenic properties in BRCA1-deficient breast cancer cells. The mechanisms underlying HspBP1-induced tumor suppression were found to include interactions with BRCA1 and promotion of BRCA1-mediated homologous recombination DNA repair, suggesting that HspBP1 contributes to the suppression of breast cancer by regulating BRCA1 function and thereby maintaining genomic stability. Interestingly, independent of BRCA1 status, HspBP1 facilitates cell survival in response to ionizing radiation (IR) by interfering with the association of Hsp70 and apoptotic protease-activating factor-1. These findings suggest that decreased HspBP1 expression, a common occurrence in high-grade and metastatic breast cancers, leads to genomic instability and enables resistance to IR treatment.https://doi.org/10.1038/s41419-022-04766-0 |
| spellingShingle | Cha Kyung Youn Jung-Hee Lee Gurusamy Hariharasudhan Hong Beum Kim Jeeho Kim Sumi Lee Sung-Chul Lim Sang-Pil Yoon Sang-Gon Park In-Youb Chang Ho Jin You HspBP1 is a dual function regulatory protein that controls both DNA repair and apoptosis in breast cancer cells Cell Death and Disease |
| title | HspBP1 is a dual function regulatory protein that controls both DNA repair and apoptosis in breast cancer cells |
| title_full | HspBP1 is a dual function regulatory protein that controls both DNA repair and apoptosis in breast cancer cells |
| title_fullStr | HspBP1 is a dual function regulatory protein that controls both DNA repair and apoptosis in breast cancer cells |
| title_full_unstemmed | HspBP1 is a dual function regulatory protein that controls both DNA repair and apoptosis in breast cancer cells |
| title_short | HspBP1 is a dual function regulatory protein that controls both DNA repair and apoptosis in breast cancer cells |
| title_sort | hspbp1 is a dual function regulatory protein that controls both dna repair and apoptosis in breast cancer cells |
| url | https://doi.org/10.1038/s41419-022-04766-0 |
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