Autophagic degradation of CDK4 is responsible for G0/G1 cell cycle arrest in NVP-BEZ235-treated neuroblastoma
Background CDK4 is highly expressed and associated with poor prognosis and decreased survival in advanced neuroblastoma (NB). Targeting CDK4 degradation presents a potentially promising therapeutic strategy compared to conventional CDK4 inhibitors. However, the autophagic degradation of the CDK4 pro...
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Taylor & Francis Group
2024-12-01
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| Series: | Cancer Biology & Therapy |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/15384047.2024.2385517 |
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| author | Zhen Liu Xiao-Yang Wang Han-Wei Wang Shan-Ling Liu Chao Zhang Feng Liu Ying Guo Feng-Hou Gao |
| author_facet | Zhen Liu Xiao-Yang Wang Han-Wei Wang Shan-Ling Liu Chao Zhang Feng Liu Ying Guo Feng-Hou Gao |
| author_sort | Zhen Liu |
| collection | DOAJ |
| description | Background CDK4 is highly expressed and associated with poor prognosis and decreased survival in advanced neuroblastoma (NB). Targeting CDK4 degradation presents a potentially promising therapeutic strategy compared to conventional CDK4 inhibitors. However, the autophagic degradation of the CDK4 protein and its anti-proliferation effect in NB cells has not been mentioned.Results We identified autophagy as a new pathway for the degradation of CDK4. Firstly, autophagic degradation of CDK4 is critical for NVP-BEZ235-induced G0/G1 arrest, as demonstrated by the overexpression of CDK4, autophagy inhibition, and blockade of autophagy-related genes. Secondly, we present the first evidence that p62 binds to CDK4 and then enters the autophagy-lysosome to degrade CDK4 in a CTSB-dependent manner in NVP-BEZ235 treated NB cells. Similar results regarding the interaction between p62 and CDK4 were observed in the NVP-BEZ235 treated NB xenograft mouse model.Conclusions Autophagic degradation of CDK4 plays a pivotal role in G0/G1 cell cycle arrest in NB cells treated with NVP-BEZ235. |
| format | Article |
| id | doaj-art-02fce2f3dc094d7e8fccb62f6aa4ddfb |
| institution | Kabale University |
| issn | 1538-4047 1555-8576 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Cancer Biology & Therapy |
| spelling | doaj-art-02fce2f3dc094d7e8fccb62f6aa4ddfb2024-12-13T06:53:24ZengTaylor & Francis GroupCancer Biology & Therapy1538-40471555-85762024-12-0125110.1080/15384047.2024.2385517Autophagic degradation of CDK4 is responsible for G0/G1 cell cycle arrest in NVP-BEZ235-treated neuroblastomaZhen Liu0Xiao-Yang Wang1Han-Wei Wang2Shan-Ling Liu3Chao Zhang4Feng Liu5Ying Guo6Feng-Hou Gao7Department of Clinical Laboratory, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, ChinaDepartment of Blood Transfusion, The Sanmenxia Central Hospital, Sanmenxia, Henan Province, ChinaDepartment of Rheumatology and Immunology, Bengbu Third People’s Hospital Affiliated to Bengbu Medical College, Bengbu, Anhui, ChinaDepartment of Clinical Laboratory, The First Hospital of Changsha City,Changsha, Hunan, ChinaDepartment of Geriatrics, Shanghai ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Oncology, Shanghai ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Pathology, Yellow River Hospital Attached Henan University of Science and Technology, Sanmenxia, Henan Province, ChinaDepartment of Oncology, Shanghai ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaBackground CDK4 is highly expressed and associated with poor prognosis and decreased survival in advanced neuroblastoma (NB). Targeting CDK4 degradation presents a potentially promising therapeutic strategy compared to conventional CDK4 inhibitors. However, the autophagic degradation of the CDK4 protein and its anti-proliferation effect in NB cells has not been mentioned.Results We identified autophagy as a new pathway for the degradation of CDK4. Firstly, autophagic degradation of CDK4 is critical for NVP-BEZ235-induced G0/G1 arrest, as demonstrated by the overexpression of CDK4, autophagy inhibition, and blockade of autophagy-related genes. Secondly, we present the first evidence that p62 binds to CDK4 and then enters the autophagy-lysosome to degrade CDK4 in a CTSB-dependent manner in NVP-BEZ235 treated NB cells. Similar results regarding the interaction between p62 and CDK4 were observed in the NVP-BEZ235 treated NB xenograft mouse model.Conclusions Autophagic degradation of CDK4 plays a pivotal role in G0/G1 cell cycle arrest in NB cells treated with NVP-BEZ235.https://www.tandfonline.com/doi/10.1080/15384047.2024.2385517CDK4autophagic degradationneuroblastomaP62NVP-BEZ235 |
| spellingShingle | Zhen Liu Xiao-Yang Wang Han-Wei Wang Shan-Ling Liu Chao Zhang Feng Liu Ying Guo Feng-Hou Gao Autophagic degradation of CDK4 is responsible for G0/G1 cell cycle arrest in NVP-BEZ235-treated neuroblastoma Cancer Biology & Therapy CDK4 autophagic degradation neuroblastoma P62 NVP-BEZ235 |
| title | Autophagic degradation of CDK4 is responsible for G0/G1 cell cycle arrest in NVP-BEZ235-treated neuroblastoma |
| title_full | Autophagic degradation of CDK4 is responsible for G0/G1 cell cycle arrest in NVP-BEZ235-treated neuroblastoma |
| title_fullStr | Autophagic degradation of CDK4 is responsible for G0/G1 cell cycle arrest in NVP-BEZ235-treated neuroblastoma |
| title_full_unstemmed | Autophagic degradation of CDK4 is responsible for G0/G1 cell cycle arrest in NVP-BEZ235-treated neuroblastoma |
| title_short | Autophagic degradation of CDK4 is responsible for G0/G1 cell cycle arrest in NVP-BEZ235-treated neuroblastoma |
| title_sort | autophagic degradation of cdk4 is responsible for g0 g1 cell cycle arrest in nvp bez235 treated neuroblastoma |
| topic | CDK4 autophagic degradation neuroblastoma P62 NVP-BEZ235 |
| url | https://www.tandfonline.com/doi/10.1080/15384047.2024.2385517 |
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