Suppression of p16 Induces mTORC1-Mediated Nucleotide Metabolic Reprogramming

Raquel Buj, Chi Wei Chen, Erika S. Dahl, Kelly E. Leon, Rostislav Kuskovsky, Natella Maglakelidze, Maithili Navaratnarajah, Gao Zhang, Mary T. Doan, Helen Jiang, Michael Zaleski, Lydia Kutzler, Holly Lacko, Yiling Lu, Gordon B. Mills, Raghavendra Gowda, Gavin P. Robertson, Joshua I. Warrick, Meenhard Herlyn, Yuka ImamuraScot R. Kimball, David J. DeGraff, Nathaniel W. Snyder, Katherine M. Aird

    Research output: Contribution to journalArticle

    4 Scopus citations

    Abstract

    Senescence bypass through p16 loss predisposes to transformation and tumorigenesis. Buj et al. found that the loss of p16 upregulates nucleotide metabolism through increased mTORC1-mediated translation of RPIA to bypass senescence in an RB-independent manner. Thus, the mTORC1-RPIA axis is a metabolic vulnerability for p16-null cancers.

    Original languageEnglish (US)
    Pages (from-to)1971-1980.e8
    JournalCell Reports
    Volume28
    Issue number8
    DOIs
    StatePublished - Aug 20 2019

    Keywords

    • BRAF
    • cancer metabolism
    • cell cycle
    • melanoma
    • nevi
    • pancreatic cancer
    • pentose phosphate pathway
    • ribonucleotide reductase M2
    • ribose-5-phosphate isomerase A
    • senescence

    ASJC Scopus subject areas

    • Biochemistry, Genetics and Molecular Biology(all)

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  • Cite this

    Buj, R., Chen, C. W., Dahl, E. S., Leon, K. E., Kuskovsky, R., Maglakelidze, N., Navaratnarajah, M., Zhang, G., Doan, M. T., Jiang, H., Zaleski, M., Kutzler, L., Lacko, H., Lu, Y., Mills, G. B., Gowda, R., Robertson, G. P., Warrick, J. I., Herlyn, M., ... Aird, K. M. (2019). Suppression of p16 Induces mTORC1-Mediated Nucleotide Metabolic Reprogramming. Cell Reports, 28(8), 1971-1980.e8. https://doi.org/10.1016/j.celrep.2019.07.084