Kinase kiểm soát 2 không cần thiết cho việc điều chỉnh phản ứng p53 nhưng cần thiết cho việc ngăn chặn G2/M và sự sống còn của tế bào trong các tế bào có khuyết tật p53 dưới stress nhiệt

Yukihiro Furusawa1,2, Yuka Yamanouchi1, Takashi Iizumi2,3, Qing-Li Zhao2, Yohei Mitsuhashi2, Akinori Morita4, Atushi Enomoto5, Yoshiaki Tabuchi6, Takashi Kondo2
1Department of Liberal Arts and Sciences, Toyama Prefectural University, Toyama, Japan
2Department of Radiological Sciences, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan
3Proton Beam Therapy Center, Tsukuba University Hospital Radiation Oncology, Tsukuba, Japan
4Department of Radiological Science, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan
5Laboratory of Molecular Radiology, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, University of Tokyo, Tokyo, Japan
6Division of Molecular Genetic Research, Life Science Research Center, University of Toyama, Toyama, Japan

Tóm tắt

Sự tăng nhiệt độ do căng thẳng nhiệt (HS) được biết đến là có khả năng ức chế sự phát triển và gây chết tế bào trong ung thư. Chúng tôi đã chứng minh rằng kinase kiểm soát 1 (Chk1) có vai trò trong việc ngăn chặn giai đoạn G2/M và sự sống còn của tế bào dưới HS; tuy nhiên, vai trò của Chk2, một đồng vận chức năng của Chk1, trong việc điều chỉnh chu kỳ tế bào và sự chết tế bào dưới HS vẫn chưa được biết đến. Ở đây, chúng tôi đã giải quyết vai trò của Chk2 bằng cách sử dụng các tế bào Molt-4 với shRNA nhắm vào p53 (Molt-4/shp53) và các tế bào kiểm soát mẹ (Molt-4/V). Ức chế Chk2 đã làm giảm acetyl hóa ở đầu C của p53 và làm chậm sự gia tăng các gen mục tiêu của p53 ở các tế bào Molt-4/V dưới HS; tuy nhiên, việc ức chế Chk2 không thể ngăn chặn sự chết tế bào do HS gây ra, cho thấy rằng Chk2 là không cần thiết cho sự chết tế bào phụ thuộc vào p53 dưới HS. Ngược lại, việc ức chế Chk2 đã làm mất đi sự ngăn chặn G2/M và thúc đẩy sự chết tế bào do HS gây ra ở các tế bào HeLa và các tế bào Molt-4/shp53. Do đó, chúng tôi đã chứng minh lần đầu tiên rằng Chk2 là cần thiết cho việc ngăn chặn chu kỳ tế bào và sự sống còn của tế bào, đặc biệt là trong các tế bào có khuyết tật p53 dưới HS. Những phát hiện này chỉ ra rằng Chk2 có thể là một mục tiêu chọn lọc cho ung thư có đột biến hoặc thiếu hụt p53 được điều trị bằng liệu pháp tăng nhiệt.

Từ khóa

#tăng nhiệt #căng thẳng nhiệt #tế bào ung thư #Chk2 #p53 #chết tế bào #ngăn chặn chu kỳ tế bào

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