Autoregulatory control of the p53 response by Siah-1L-mediated HIPK2 degradation

Marco A. Calzado, Laureano de la Vega, Eduardo Muñoz, M. Lienhard Schmitz (Lead / Corresponding author)

    Research output: Contribution to journalArticle

    7 Citations (Scopus)

    Abstract

    The different activities of the tumor suppressor p53 are tightly regulated by various negative and positive feedback loops, which allow accurate control of its function. Here we show that the p53-inducible ubiquitin E3 ligase Siah-1L can bind to the p53 phosphorylating kinase HIPK2 and thus allows its ubiquitination and proteasomal elimination. Siah-1L also eliminates the HIPK family member HIPK3, indicating that its activity is not restricted to one member of the HIPK family. The stimulating effect of HIPK2 on p53-triggered transcription is counteracted by Siah-1L, thus showing the occurrence of another negative feedback loop controlling the p53 response.

    Original languageEnglish
    Pages (from-to)1079-1083
    Number of pages5
    JournalBiological Chemistry
    Volume390
    Issue number10
    Early online date30 Jul 2009
    DOIs
    Publication statusPublished - Oct 2009

    Keywords

    • Apoptosis
    • Base sequence
    • Carrier proteins
    • Cell line
    • Down-regulation
    • Humans
    • Nuclear proteins
    • Polyubiquitin
    • Protein-Serine-Threonine Kinases
    • Transcription, Genetic
    • Tumor suppressor protein p53
    • Ubiquitin-Protein Ligases
    • Up-regulation

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