Targeting the ubiquitin-proteasome system to activate wild-type p53 for cancer therapy.
Ubiquitination plays a key role in regulating the tumour suppressor p53. It targets p53 for degradation by the 26S proteasome. The ubiquitin pathway also regulates the activity and localisation of p53. Ubiquitination requires ubiquitin-activating and -conjugating enzymes and ubiquitin ligases. In addition, ubiquitination can be reversed by the action of deubiquitinating enzymes. Here we give an overview of the role of components of the ubiquitin-proteasome system in the regulation of p53 and review progress in targeting these proteins to activate wild-type p53 for the treatment of cancer.
Allende-Vega
Nerea
N
CR-UK Cell Transformation Research Group, Department of Surgery and Molecular Oncology, Ninewells Hospital and Medical School, University of Dundee, Dundee, Scotland, United Kingdom.
Saville
Mark K
MK
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D025801:Ubiquitin / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*
D000970:Antineoplastic Agents; D016159:Tumor Suppressor Protein p53; D025801:Ubiquitin; D044767:Ubiquitin-Protein Ligases; D046988:Proteasome Endopeptidase Complex