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Positive interactions between STAP-1 and BCR-ABL influence chronic myeloid leukemia cell proliferation and survival
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Title: | Positive interactions between STAP-1 and BCR-ABL influence chronic myeloid leukemia cell proliferation and survival |
Authors: | Ishiura, Marie Browse this author | Kitai, Yuichi Browse this author →KAKEN DB | Kashiwakura, Jun-ichi Browse this author →KAKEN DB | Muromoto, Ryuta Browse this author →KAKEN DB | Toda, Jun Browse this author | Ichii, Michiko Browse this author | Oritani, Kenji Browse this author →KAKEN DB | Matsuda, Tadashi Browse this author →KAKEN DB |
Keywords: | CML | BCR-ABL | STAP-1 | STAT5 | NFAT |
Issue Date: | 4-Jun-2021 |
Publisher: | Elsevier |
Journal Title: | Biochemical and biophysical research communications |
Volume: | 556 |
Start Page: | 185 |
End Page: | 191 |
Publisher DOI: | 10.1016/j.bbrc.2021.03.162 |
Abstract: | Chronic myeloid leukemia (CML) is a clonal disease characterized by the presence of the Philadelphia chromosome and its oncogenic product, BCR-ABL, which activates multiple pathways involved in cell survival, growth promotion, and disease progression. We recently reported that signal-transducing adaptor protein 1 (STAP-1) is upregulated in CML stem cells (LSCs) and functions to reduce the apoptosis of CML LSCs by upregulating the STAT5-downstream anti-apoptotic genes. In this study, we demonstrate the detailed molecular interactions among BCR-ABL, STAP-1, and signal transducer and activator of transcription 5 (STAT5). Studies with deletion mutants have revealed that STAP-1 interacts with BCR-ABL and STAT5a through its SH2 and PH domains, respectively, suggesting the possible role of STAP-1 as a scaffold protein. Furthermore, the binding of STAP-1 to BCR-ABL stabilizes the BCR-ABL protein in CML cells. Since STAP-1 is highly expressed in CML cells, we also analyzed the STAP-1 promoter activity using a luciferase reporter construct and found that NFATc1 is involved in activating the STAP-1 promoter and inducing STAP-1 mRNA expression. Our results demonstrate that STAP-1 contributes to the BCR-ABL/STAT5 and BCR-ABL/Ca2+/NFAT signals to induce proliferation and STAP-1 mRNA expression in CML cells, respectively. |
Rights: | © <2021>. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/ | http://creativecommons.org/licenses/by-nc-nd/4.0/ |
Type: | article (author version) |
URI: | http://hdl.handle.net/2115/86122 |
Appears in Collections: | 薬学研究院 (Faculty of Pharmaceutical Sciences) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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Submitter: 松田 正
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