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 Imamura; Scot R. Kimball; David J. DeGraff; Nathaniel W. Snyder; Katherine M. Aird

doi:10.1016/j.celrep.2019.07.084

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 journal › Article

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 language	English (US)
Pages (from-to)	1971-1980.e8
Journal	Cell Reports
Volume	28
Issue number	8
DOIs	https://doi.org/10.1016/j.celrep.2019.07.084
State	Published - 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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10.1016/j.celrep.2019.07.084

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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

Suppression of p16 Induces mTORC1-Mediated Nucleotide Metabolic Reprogramming. / Buj, Raquel; Chen, Chi Wei; Dahl, Erika S.; Leon, Kelly E.; Kuskovsky, Rostislav; Maglakelidze, Natella; Navaratnarajah, Maithili; Zhang, Gao; Doan, Mary T.; Jiang, Helen; Zaleski, Michael; Kutzler, Lydia; Lacko, Holly; Lu, Yiling; Mills, Gordon B.; Gowda, Raghavendra; Robertson, Gavin P.; Warrick, Joshua I.; Herlyn, Meenhard; Imamura, Yuka; Kimball, Scot R.; DeGraff, David J.; Snyder, Nathaniel W.; Aird, Katherine M.

In: Cell Reports, Vol. 28, No. 8, 20.08.2019, p. 1971-1980.e8.

Research output: Contribution to journal › Article

Buj, R, Chen, CW, Dahl, ES, Leon, KE, Kuskovsky, R, Maglakelidze, N, Navaratnarajah, M, Zhang, G, Doan, MT, Jiang, H, Zaleski, M, Kutzler, L, Lacko, H, Lu, Y, Mills, GB, Gowda, R, Robertson, GP, Warrick, JI, Herlyn, M, Imamura, Y, Kimball, SR, DeGraff, DJ, Snyder, NW & Aird, KM 2019, 'Suppression of p16 Induces mTORC1-Mediated Nucleotide Metabolic Reprogramming', Cell Reports, vol. 28, no. 8, pp. 1971-1980.e8. https://doi.org/10.1016/j.celrep.2019.07.084

Buj, Raquel ; Chen, Chi Wei ; Dahl, Erika S. ; Leon, Kelly E. ; Kuskovsky, Rostislav ; Maglakelidze, Natella ; Navaratnarajah, Maithili ; Zhang, Gao ; Doan, Mary T. ; Jiang, Helen ; Zaleski, Michael ; Kutzler, Lydia ; Lacko, Holly ; Lu, Yiling ; Mills, Gordon B. ; Gowda, Raghavendra ; Robertson, Gavin P. ; Warrick, Joshua I. ; Herlyn, Meenhard ; Imamura, Yuka ; Kimball, Scot R. ; DeGraff, David J. ; Snyder, Nathaniel W. ; Aird, Katherine M. / Suppression of p16 Induces mTORC1-Mediated Nucleotide Metabolic Reprogramming. In: Cell Reports. 2019 ; Vol. 28, No. 8. pp. 1971-1980.e8.

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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.",

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