Tính không thể đảo ngược của sự già hóa tế bào: vai trò kép của con đường p16INK4a/Rb trong kiểm soát chu kỳ tế bào

Akiko Takahashi1, Naoko Ohtani1, Eiji Hara1
1Division of Protein Information, Institute for Genome Research, University of Tokushima, 3-18-15 Kuramoto-cho, Tokushima, 770-8503, Japan

Tóm tắt

Tóm tắt

Gen ức chế u retinoblastoma (Rb), sản phẩm protein pRb, đã được xác định có vai trò trong việc thiết lập tình trạng già hóa tế bào, trạng thái ngừng chu kỳ tế bào G1 không thể đảo ngược do nhiều căng thẳng gây ung thư khác nhau. Trong các tế bào chuột, sự ngừng chu kỳ tế bào già hóa có thể được đảo ngược bằng cách làm bất hoạt pRb sau đó, cho thấy rằng pRb không chỉ cần thiết cho sự khởi đầu của sự già hóa tế bào mà còn cho việc duy trì chương trình già hóa trong các tế bào chuột. Tuy nhiên, ở các tế bào người, một khi pRb được kích hoạt hoàn toàn bởi p16INK4a, sự ngừng chu kỳ tế bào già hóa trở nên không thể đảo ngược và không còn bị đảo ngược bởi việc làm bất hoạt pRb sau đó, điều này gợi ý rằng con đường p16INK4a/Rb kích hoạt một cơ chế thay thế để ngăn chặn chu kỳ tế bào một cách không thể đảo ngược trong các tế bào người đã già hóa. Ở đây, chúng tôi thảo luận về cơ chế phân tử nền tảng cho tính không thể đảo ngược của sự ngừng chu kỳ tế bào già hóa và tiềm năng của nó đối với việc ức chế khối u.

Từ khóa


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