RNF144A-VRK2-G3BP1 axis regulates stress granule assembly
Abstract Under the cellular stress, stress granules (SGs) help survival and proliferation of the cell. Unfortunately, the same SGs help unwanted cancer cells under stressful environment, including anti-cancer chemotherapy treatment. While SGs elevate the cancer cell’s resistance to chemotherapy, the...
Saved in:
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Publishing Group
2025-04-01
|
| Series: | Cell Death Discovery |
| Online Access: | https://doi.org/10.1038/s41420-025-02460-6 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850184410153877504 |
|---|---|
| author | Sung Wook Kim Jae Lee Kyung Won Jo Young-Hun Jeong Won Sik Shin Kyong-Tai Kim |
| author_facet | Sung Wook Kim Jae Lee Kyung Won Jo Young-Hun Jeong Won Sik Shin Kyong-Tai Kim |
| author_sort | Sung Wook Kim |
| collection | DOAJ |
| description | Abstract Under the cellular stress, stress granules (SGs) help survival and proliferation of the cell. Unfortunately, the same SGs help unwanted cancer cells under stressful environment, including anti-cancer chemotherapy treatment. While SGs elevate the cancer cell’s resistance to chemotherapy, the mechanism behind the formation of SGs in cancer cell under chemotherapy treatment is still to be revealed. Here, we identified that the level of VRK2 and the phosphorylation of its novel substrate, G3BP1, are reduced when the cellular stress was increased by sodium arsenite (SA) or cisplatin treatment. We also demonstrated that the level of RNF144A is increased in response to the stress and further downregulates VRK2 through proteasomal degradation in various types of cancer cells. Furthermore, inhibition of SG formation by the overexpression of VRK2 sensitized the cells to the stress and chemotherapy. Together, our study establishes an RNF144A-VRK2-G3BP1 axis that regulates SG formation and suggest its potential usage in anti-cancer therapy. |
| format | Article |
| id | doaj-art-599764c9151d4131b2cac4eef42896f2 |
| institution | OA Journals |
| issn | 2058-7716 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death Discovery |
| spelling | doaj-art-599764c9151d4131b2cac4eef42896f22025-08-20T02:17:04ZengNature Publishing GroupCell Death Discovery2058-77162025-04-0111111310.1038/s41420-025-02460-6RNF144A-VRK2-G3BP1 axis regulates stress granule assemblySung Wook Kim0Jae Lee1Kyung Won Jo2Young-Hun Jeong3Won Sik Shin4Kyong-Tai Kim5Department of Life Sciences, Pohang University of Science and TechnologyDepartment of Life Sciences, Pohang University of Science and TechnologyHesed Bio CorporationDepartment of Life Sciences, Pohang University of Science and TechnologyDepartment of Life Sciences, Pohang University of Science and TechnologyGenerative Genomics Research Center, Global Green Research & Development Center, Handong Global UniversityAbstract Under the cellular stress, stress granules (SGs) help survival and proliferation of the cell. Unfortunately, the same SGs help unwanted cancer cells under stressful environment, including anti-cancer chemotherapy treatment. While SGs elevate the cancer cell’s resistance to chemotherapy, the mechanism behind the formation of SGs in cancer cell under chemotherapy treatment is still to be revealed. Here, we identified that the level of VRK2 and the phosphorylation of its novel substrate, G3BP1, are reduced when the cellular stress was increased by sodium arsenite (SA) or cisplatin treatment. We also demonstrated that the level of RNF144A is increased in response to the stress and further downregulates VRK2 through proteasomal degradation in various types of cancer cells. Furthermore, inhibition of SG formation by the overexpression of VRK2 sensitized the cells to the stress and chemotherapy. Together, our study establishes an RNF144A-VRK2-G3BP1 axis that regulates SG formation and suggest its potential usage in anti-cancer therapy.https://doi.org/10.1038/s41420-025-02460-6 |
| spellingShingle | Sung Wook Kim Jae Lee Kyung Won Jo Young-Hun Jeong Won Sik Shin Kyong-Tai Kim RNF144A-VRK2-G3BP1 axis regulates stress granule assembly Cell Death Discovery |
| title | RNF144A-VRK2-G3BP1 axis regulates stress granule assembly |
| title_full | RNF144A-VRK2-G3BP1 axis regulates stress granule assembly |
| title_fullStr | RNF144A-VRK2-G3BP1 axis regulates stress granule assembly |
| title_full_unstemmed | RNF144A-VRK2-G3BP1 axis regulates stress granule assembly |
| title_short | RNF144A-VRK2-G3BP1 axis regulates stress granule assembly |
| title_sort | rnf144a vrk2 g3bp1 axis regulates stress granule assembly |
| url | https://doi.org/10.1038/s41420-025-02460-6 |
| work_keys_str_mv | AT sungwookkim rnf144avrk2g3bp1axisregulatesstressgranuleassembly AT jaelee rnf144avrk2g3bp1axisregulatesstressgranuleassembly AT kyungwonjo rnf144avrk2g3bp1axisregulatesstressgranuleassembly AT younghunjeong rnf144avrk2g3bp1axisregulatesstressgranuleassembly AT wonsikshin rnf144avrk2g3bp1axisregulatesstressgranuleassembly AT kyongtaikim rnf144avrk2g3bp1axisregulatesstressgranuleassembly |