CDK-dependent phosphorylation of PHD1 on serine 130 alters its substrate preference in cells

Brian Ortmann, Dalila Bensaddek, Sara Carvalhal, Sandra C Moser, Sharon Mudie, Eric R Griffis, Jason R Swedlow, Angus I Lamond, Sonia Rocha (Lead / Corresponding author)

    Research output: Contribution to journalArticlepeer-review

    15 Citations (Scopus)
    253 Downloads (Pure)


    PHD1 (also known as EGLN2) belongs to a family of prolyl hydroxylases (PHDs) that are involved in the control of the cellular response to hypoxia. PHD1 is also able to regulate mitotic progression through the regulation of the crucial centrosomal protein Cep192, establishing a link between the oxygen-sensing and the cell cycle machinery. Here, we demonstrate that PHD1 is phosphorylated by CDK2, CDK4 and CDK6 at S130. This phosphorylation fluctuates with the cell cycle and can be induced through oncogenic activation. Functionally, PHD1 phosphorylation leads to increased induction of hypoxia-inducible factor (HIF) protein levels and activity during hypoxia. PHD1 phosphorylation does not alter its intrinsic enzymatic activity, but instead decreases the interaction between PHD1 and HIF1α. Interestingly, although phosphorylation of PHD1 at S130 lowers its activity towards HIF1α, this modification increases the activity of PHD1 towards Cep192. These results establish a mechanism by which cell cycle mediators, such as CDKs, temporally control the activity of PHD1, directly altering the regulation of HIF1α and Cep192.

    Original languageEnglish
    Pages (from-to)191-205
    Number of pages15
    JournalJournal of Cell Science
    Issue number1
    Early online date4 Jan 2016
    Publication statusPublished - Jan 2016


    • EGLN2
    • HIF
    • Cep192
    • Hypoxia


    Dive into the research topics of 'CDK-dependent phosphorylation of PHD1 on serine 130 alters its substrate preference in cells'. Together they form a unique fingerprint.

    Cite this