Các yếu tố phiên mã FoxO động học
Tóm tắt
Các yếu tố phiên mã hộp Forkhead O (FoxO) bao gồm FoxO1, FoxO3a, FoxO4 và FoxO6, là các đồng loại động vật có vú của DAF-16 ở Caenorhabditis elegans, đang nổi lên như một họ protein quan trọng điều chỉnh biểu hiện của các gen liên quan đến apoptosis, chu kỳ tế bào, sửa chữa DNA, căng thẳng oxy hóa, phân hóa tế bào, chuyển hóa glucose và các chức năng tế bào khác. Các protein FoxO được điều chỉnh bởi nhiều cơ chế khác nhau. Chúng trải qua phosphoryl hóa ức chế bởi các kinase protein như Akt, SGK, IKK và CDK2 dưới tác động của các kích thích bên ngoài và bên trong. Ngược lại, chúng được kích hoạt bởi các yếu tố điều hòa thượng nguồn như JNK và MST1 trong điều kiện căng thẳng. Hoạt động của chúng được cân bằng bởi các acetylase CBP và p300 cùng với deacetylase SIRT1. Hơn nữa, trong khi polyubiquitylation của FoxO1 và FoxO3a dẫn đến sự phân hủy của chúng bởi proteasome, monoubiquitylation của FoxO4 lại tạo điều kiện cho sự định vị trong nhân và tăng cường hoạt động phiên mã của nó. Do đó, các chức năng mạnh mẽ của các protein FoxO được kiểm soát chặt chẽ bởi các con đường tín hiệu phức tạp trong các điều kiện sinh lý; sự điều hòa bất thường của các protein này có thể dẫn đến bệnh tật như ung thư.
Từ khóa
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