Making Connections: p53 and the Cathepsin Proteases as Co-Regulators of Cancer and Apoptosis

Cancers

VladimirA Makarov¹  AndreyAZamyatnin¹  SurinderM Soond¹  LyudmilaV Savvateeva¹  NeonilaV Gorokhovets¹  PaulA Townsend² 

[1]Institute of Molecular Medicine, Sechenov First Moscow State Medical University, Trubetskaya str. 8-2, 119991 Moscow, Russia

[2]Manchester Academic Health Science Centre, the NIHR Manchester Biomedical Research Centre, Division of Cancer Sciences and Manchester Cancer Research Centre, Faculty of Biology, Medicine and Health, University of Manchester, Manchester M13 9PL, UK

关键词: p53;    cathepsin;    cancer;    MOMP;    apoptosis;    lysosomal membrane permeabilization;   

DOI  :  10.3390/cancers12113476

来源: DOAJ

【 摘 要 】

While viewed as the “guardian of the genome”, the importance of the tumor suppressor p53 protein has increasingly gained ever more recognition in modulating additional modes of action related to cell death. Slowly but surely, its importance has evolved from a mutated genetic locus heavily implicated in a wide array of cancer types to modulating lysosomal-mediated cell death either directly or indirectly through the transcriptional regulation of the key signal transduction pathway intermediates involved in this. As an important step in determining the fate of cells in response to cytotoxicity or during stress response, lysosomal-mediated cell death has also become strongly interwoven with the key components that give the lysosome functionality in the form of the cathepsin proteases. While a number of articles have been published highlighting the independent input of p53 or cathepsins to cellular homeostasis and disease progression, one key area that warrants further focus is the regulatory relationship that p53 and its isoforms share with such proteases in regulating lysosomal-mediated cell death. Herein, we review recent developments that have shaped this relationship and highlight key areas that need further exploration to aid novel therapeutic design and intervention strategies.

【 授权许可】

Unknown