PRL stimulates mitotic errors by suppressing kinetochore-localized activation of AMPK during mitosis
Phosphatase of regenerating liver (PRL) is frequently overexpressed in various malignant cancers and is known to be a driver of malignancy. Here, we demonstrated that PRL overexpression causes mitotic errors that accompany spindle misorientation and aneuploidy, which are intimately associated with c...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Japan Society for Cell Biology
2022-11-01
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| Series: | Cell Structure and Function |
| Subjects: | |
| Online Access: | https://www.jstage.jst.go.jp/article/csf/47/2/47_22034/_html/-char/en |
| _version_ | 1797695382767009792 |
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| author | Kajung Ryu Atsushi Yoshida Yosuke Funato Daisuke Yamazaki Hiroaki Miki |
| author_facet | Kajung Ryu Atsushi Yoshida Yosuke Funato Daisuke Yamazaki Hiroaki Miki |
| author_sort | Kajung Ryu |
| collection | DOAJ |
| description | Phosphatase of regenerating liver (PRL) is frequently overexpressed in various malignant cancers and is known to be a driver of malignancy. Here, we demonstrated that PRL overexpression causes mitotic errors that accompany spindle misorientation and aneuploidy, which are intimately associated with cancer progression. Mechanistic analyses of this phenomenon revealed dysregulation of the energy sensor kinase, AMP-activated protein kinase (AMPK), in PRL-induced mitotic errors. Specifically, immunofluorescence analysis showed that levels of phosphorylated AMPK (P-AMPK), an activated form of AMPK, at the kinetochore were reduced by PRL expression. Moreover, artificial activation of AMPK using chemical activators, such as A769662 and AICAR, in PRL-expressing cells restored P-AMPK signals at the kinetochore and normalized spindle orientation. Collectively, these results indicate the crucial importance of the activation of kinetochore-localized AMPK in the normal progression of mitosis, which is specifically perturbed by PRL overexpression. Key words: cancer, AMPK, PRL, kinetochore, mitotic errors |
| first_indexed | 2024-03-12T03:10:39Z |
| format | Article |
| id | doaj.art-d616a418b3994ef1b2421e2b1d58c39a |
| institution | Directory Open Access Journal |
| issn | 0386-7196 1347-3700 |
| language | English |
| last_indexed | 2024-03-12T03:10:39Z |
| publishDate | 2022-11-01 |
| publisher | Japan Society for Cell Biology |
| record_format | Article |
| series | Cell Structure and Function |
| spelling | doaj.art-d616a418b3994ef1b2421e2b1d58c39a2023-09-03T14:26:33ZengJapan Society for Cell BiologyCell Structure and Function0386-71961347-37002022-11-01472758710.1247/csf.22034csfPRL stimulates mitotic errors by suppressing kinetochore-localized activation of AMPK during mitosisKajung Ryu0Atsushi Yoshida1Yosuke Funato2Daisuke Yamazaki3Hiroaki Miki4Department of Cellular Regulation, Research Institute for Microbial Diseases, Osaka UniversityDepartment of Cellular Regulation, Research Institute for Microbial Diseases, Osaka UniversityDepartment of Cellular Regulation, Research Institute for Microbial Diseases, Osaka UniversityDepartment of Cellular Regulation, Research Institute for Microbial Diseases, Osaka UniversityDepartment of Cellular Regulation, Research Institute for Microbial Diseases, Osaka UniversityPhosphatase of regenerating liver (PRL) is frequently overexpressed in various malignant cancers and is known to be a driver of malignancy. Here, we demonstrated that PRL overexpression causes mitotic errors that accompany spindle misorientation and aneuploidy, which are intimately associated with cancer progression. Mechanistic analyses of this phenomenon revealed dysregulation of the energy sensor kinase, AMP-activated protein kinase (AMPK), in PRL-induced mitotic errors. Specifically, immunofluorescence analysis showed that levels of phosphorylated AMPK (P-AMPK), an activated form of AMPK, at the kinetochore were reduced by PRL expression. Moreover, artificial activation of AMPK using chemical activators, such as A769662 and AICAR, in PRL-expressing cells restored P-AMPK signals at the kinetochore and normalized spindle orientation. Collectively, these results indicate the crucial importance of the activation of kinetochore-localized AMPK in the normal progression of mitosis, which is specifically perturbed by PRL overexpression. Key words: cancer, AMPK, PRL, kinetochore, mitotic errorshttps://www.jstage.jst.go.jp/article/csf/47/2/47_22034/_html/-char/encancerampkprlkinetochoremitotic errors |
| spellingShingle | Kajung Ryu Atsushi Yoshida Yosuke Funato Daisuke Yamazaki Hiroaki Miki PRL stimulates mitotic errors by suppressing kinetochore-localized activation of AMPK during mitosis Cell Structure and Function cancer ampk prl kinetochore mitotic errors |
| title | PRL stimulates mitotic errors by suppressing kinetochore-localized activation of AMPK during mitosis |
| title_full | PRL stimulates mitotic errors by suppressing kinetochore-localized activation of AMPK during mitosis |
| title_fullStr | PRL stimulates mitotic errors by suppressing kinetochore-localized activation of AMPK during mitosis |
| title_full_unstemmed | PRL stimulates mitotic errors by suppressing kinetochore-localized activation of AMPK during mitosis |
| title_short | PRL stimulates mitotic errors by suppressing kinetochore-localized activation of AMPK during mitosis |
| title_sort | prl stimulates mitotic errors by suppressing kinetochore localized activation of ampk during mitosis |
| topic | cancer ampk prl kinetochore mitotic errors |
| url | https://www.jstage.jst.go.jp/article/csf/47/2/47_22034/_html/-char/en |
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