Targeting the ubiquitin-proteasome system to activate wild-type p53 for cancer therapy

Nerea Allende-Vega, Mark K. Saville

    Research output: Contribution to journalReview article

    33 Citations (Scopus)

    Abstract

    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. (C) 2009 Published by Elsevier Ltd.

    Original languageEnglish
    Pages (from-to)29-39
    Number of pages11
    JournalSeminars in Cancer Biology
    Volume20
    Issue number1
    DOIs
    Publication statusPublished - Feb 2010

    Keywords

    • Ubiquitin
    • P53
    • Mdm2
    • MdmX
    • 26S proteasome
    • E1
    • E2
    • E3
    • Deubiquitinating enzyme
    • SMALL-MOLECULE INHIBITORS
    • EARLY EMBRYONIC LETHALITY
    • TUMOR-SUPPRESSOR PROTEIN
    • CELL-CYCLE ARREST
    • IN-VIVO
    • DNA-DAMAGE
    • LIGASE ACTIVITY
    • PROSTATE-CANCER
    • MDM2 PROMOTES
    • COLON-CANCER

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