Cezanne (OTUD7B) regulates HIF-1α homeostasis in a proteasome-independent manner

Anja Bremm (Lead / Corresponding author), Sonia Moniz, Julia Mader, Sonia Rocha (Lead / Corresponding author), David Komander (Lead / Corresponding author)

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    Abstract

    The transcription factor HIF-1α is essential for cells to rapidly adapt to low oxygen levels (hypoxia). HIF-1α is frequently deregulated in cancer and correlates with poor patient prognosis. Here, we demonstrate that the deubiquitinase Cezanne regulates HIF-1α homeostasis. Loss of Cezanne decreases HIF-1α target gene expression due to a reduction in HIF-1α protein levels. Surprisingly, although the Cezanne-regulated degradation of HIF-1α depends on the tumour suppressor pVHL, hydroxylase and proteasome activity are dispensable. Our data suggest that Cezanne is essential for HIF-1α protein stability and that loss of Cezanne stimulates HIF-1α degradation via proteasome-independent routes, possibly through chaperone-mediated autophagy.

    Original languageEnglish
    Pages (from-to)1268-1277
    Number of pages10
    JournalEMBO Reports
    Volume15
    Issue number12
    DOIs
    Publication statusPublished - 1 Dec 2014

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    Bremm, A., Moniz, S., Mader, J., Rocha, S., & Komander, D. (2014). Cezanne (OTUD7B) regulates HIF-1α homeostasis in a proteasome-independent manner. EMBO Reports, 15(12), 1268-1277. https://doi.org/10.15252/embr.201438850