Tribbles pseudokinase 3 regulation and contribution to cancer

Bojana Stefanovska, Fabrice André, Olivia Fromigué

    Research output: Contribution to journalReview articlepeer-review

    27 Citations (Scopus)

    Abstract

    The first Tribbles protein was identified as critical for the coordination of morphogenesis in Drosophila melanogaster. Three mammalian homologs were subsequently identified, with a structure similar to classic serine/threonine kinases, but lacking crucial amino acids for the catalytic activity. Thereby, the very weak ATP affinity classifies TRIB proteins as pseudokinases. In this review, we provide an overview of the regulation of TRIB3 gene expression at both transcriptional and post-translational levels. Despite the absence of kinase activity, TRIB3 interferes with a broad range of cellular processes through protein–protein interactions. In fact, TRIB3 acts as an adaptor/scaffold protein for many other proteins such as kinase-dependent proteins, transcription factors, ubiquitin ligases, or even components of the spliceosome machinery. We then state the contribution of TRIB3 to cancer development, progression, and metastasis. TRIB3 dysregulation can be associated with good or bad prognosis. Indeed, as TRIB3 interacts with and regulates the activity of many key signaling components, it can act as a tumor-suppressor or oncogene in a context-dependent manner.

    Original languageEnglish
    Article number1822
    JournalCancers
    Volume13
    Issue number8
    DOIs
    Publication statusPublished - 2 Apr 2021

    Keywords

    • Akt
    • ER stress
    • FK506 binding protein
    • MTOR
    • Oncogene
    • Pseudokinase
    • RNA splicing
    • Rapamycin
    • Signaling pathway
    • Tumor suppressor

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