FKBP25, a novel regulator of the p53 pathway, induces the degradation of MDM2 and activation of p53

Anna Maria Ochocka, Petros Kampanis, Samantha Nicol, Nerea Allende-Vega, Miranda Cox, Lynnette Marcar, Diane Milne, Frances Fuller-Pace, David Meek

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    48 Citations (Scopus)


    The p53 tumour suppressor protein is tightly controlled by the E3 ubiquitin ligase, mouse double minute 2 (MDM2), but maintains MDM2 expression as part of a negative feedback loop. We have identified the immunophilin, 25 kDa FK506-binding protein (FKBP25), previously shown to be regulated by p53-mediated repression, as an MDM2-interacting partner. We show that FKBP25 stimulates auto-ubiquitylation and proteasomal degradation of MDM2, leading to the induction of p53. Depletion of FKBP25 by siRNA leads to increased levels of MDM2 and a corresponding reduction in p53 and p21 levels. These data are consistent with the idea that FKBP25 contributes to regulation of the p53-MDM2 negative feedback loop. (C) 2009 Federation of European Biochemical Societies. Published by Elsevier B. V. All rights reserved.

    Original languageEnglish
    Pages (from-to)621-626
    Number of pages6
    JournalFEBS Letters
    Issue number4
    Publication statusPublished - 18 Feb 2009


    • FKBP25
    • MDM2
    • p53
    • E3 ligase
    • Ubiquitylation
    • Degradation
    • IN-VITRO

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