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NCAPH, ubiquitinated by TRIM21, promotes cell proliferation by inhibiting autophagy of cervical cancer through AKT/mTOR dependent signaling.
Wang, Shiqi; Qiao, Xiaowen; Cui, Yaqi; Liu, Liang; Cooper, Tamara; Hu, Yingxin; Lin, Jiaxiang; Liu, Haiting; Wang, Meng; Hayball, John; Wang, Xiao.
Afiliación
  • Wang S; Department of Pathology, School of Basic Medical Sciences and Qilu Hospital, Shandong University, Jinan, Shandong Province, China.
  • Qiao X; Department of Pathology, School of Basic Medical Sciences and Qilu Hospital, Shandong University, Jinan, Shandong Province, China.
  • Cui Y; Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Gastrointestinal Surgery IV, Peking University Cancer Hospital & Institute, Beijing, 100142, China.
  • Liu L; Department of Pathology, School of Basic Medical Sciences and Qilu Hospital, Shandong University, Jinan, Shandong Province, China.
  • Cooper T; Experimental Therapeutics Laboratory, School of Pharmacy and Medical Sciences, University of South Australia Cancer Research Institute, Adelaide, SA, Australia.
  • Hu Y; Experimental Therapeutics Laboratory, School of Pharmacy and Medical Sciences, University of South Australia Cancer Research Institute, Adelaide, SA, Australia.
  • Lin J; Department of Pathology, School of Basic Medical Sciences and Qilu Hospital, Shandong University, Jinan, Shandong Province, China.
  • Liu H; Department of Pathology, School of Basic Medical Sciences and Qilu Hospital, Shandong University, Jinan, Shandong Province, China.
  • Wang M; Department of Pathology, School of Basic Medical Sciences and Qilu Hospital, Shandong University, Jinan, Shandong Province, China.
  • Hayball J; Department of Pathology, School of Basic Medical Sciences and Qilu Hospital, Shandong University, Jinan, Shandong Province, China.
  • Wang X; Experimental Therapeutics Laboratory, School of Pharmacy and Medical Sciences, University of South Australia Cancer Research Institute, Adelaide, SA, Australia.
Cell Death Dis ; 15(8): 565, 2024 Aug 06.
Article en En | MEDLINE | ID: mdl-39103348
ABSTRACT
Autophagy is closely related to the occurrence and development of human malignancies; however, the detailed mechanisms underlying autophagy in cervical cancer require further investigation. Previously, we found that the ectopic expression of NCAPH, a regulatory subunit of condensed protein complexes, significantly enhanced the proliferation of tumor cells; however, the underlying mechanisms were unclear. Here, we revealed that NCAPH is a novel autophagy-associated protein in cervical cancer that promotes cell proliferation by inhibiting autophagosome formation and reducing autophagy, with no effect on the cell cycle, apoptosis, or aging. Tripartite motif-containing protein 21 (TRIM21) is well known to be involved in inflammation, autoimmunity and cancer, mainly via its E3 ubiquitin ligase activity. Mass spectrometry and immunoprecipitation assays showed that TRIM21 interacted with NCAPH and decreased the protein stability of NCAPH via ubiquitination at the K11 lysine residue. Structural domain mutation analysis revealed that TRIM21 combined with NCAPH through its PRY/SPRY and CC domains and accelerated the degradation of NCAPH through the RING domain. Furthermore, TRIM21 promoted autophagosome formation and reduced cell proliferation by inhibiting NCAPH expression and the downstream AKT/mTOR pathway in cervical cancer cells. Immunohistochemical staining revealed that the protein expression of TRIM21 was negatively correlated with that of NCAPH and positively correlated with that of beclin-1 in cervical cancer tissues. Therefore, we provide evidence for the role of the TRIM21-NCAPH axis in cervical cancer autophagy and proliferation and the involvement of the AKT/mTOR signaling pathway in this process. These results deepen our understanding of the carcinogenesis of cervical cancer, broaden the understanding of the molecular mechanisms of TRIM21 and NCAPH, and provide guidance for individualized treatment of cervical cancer in the future.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Ribonucleoproteínas / Autofagia / Transducción de Señal / Neoplasias del Cuello Uterino / Proliferación Celular / Proteínas Proto-Oncogénicas c-akt / Ubiquitinación / Serina-Treonina Quinasas TOR Límite: Animals / Female / Humans Idioma: En Revista: Cell Death Dis Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Ribonucleoproteínas / Autofagia / Transducción de Señal / Neoplasias del Cuello Uterino / Proliferación Celular / Proteínas Proto-Oncogénicas c-akt / Ubiquitinación / Serina-Treonina Quinasas TOR Límite: Animals / Female / Humans Idioma: En Revista: Cell Death Dis Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido