P53/TAp63 and AKT regulate mammalian target of rapamycin complex 1 (mTORC1) signaling through two independent parallel pathways in the presence of DNA damage

Maren Cam; Hemant K. Bid; Linlin Xiao; Gerard P. Zambetti; Peter J. Houghton; Hakan Cam

doi:10.1074/jbc.M113.530303

P53/TAp63 and AKT regulate mammalian target of rapamycin complex 1 (mTORC1) signaling through two independent parallel pathways in the presence of DNA damage

Maren Cam, Hemant K. Bid, Linlin Xiao, Gerard P. Zambetti, Peter J. Houghton, Hakan Cam

Molecular Medicine

Research output: Contribution to journal › Article

37 Scopus citations

Abstract

Background: mTORC1 integrates cellular inputs and is often deregulated in cancer. Results: In response to DNA damage, p53/TAp63 and AKT regulate mTORC1 through two independent parallel pathways. Conclusion: DNA damage activates Akt, resulting in inhibition of S6K1, whereas Sestrin1/2 downstream of p53 and REDD1 downstream of p63 coordinate to suppress 4E-BP1. Significance: mTORC1-dependent 4EBP1 inhibition by DNA damage is abrogated in most human cancers.

Original language	English (US)
Pages (from-to)	4083-4094
Number of pages	12
Journal	Journal of Biological Chemistry
Volume	289
Issue number	7
DOIs	https://doi.org/10.1074/jbc.M113.530303
State	Published - Feb 14 2014

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ASJC Scopus subject areas

Biochemistry
Molecular Biology
Cell Biology

Cite this

Cam, M., Bid, H. K., Xiao, L., Zambetti, G. P., Houghton, P. J., & Cam, H. (2014). P53/TAp63 and AKT regulate mammalian target of rapamycin complex 1 (mTORC1) signaling through two independent parallel pathways in the presence of DNA damage. Journal of Biological Chemistry, 289(7), 4083-4094. https://doi.org/10.1074/jbc.M113.530303

P53/TAp63 and AKT regulate mammalian target of rapamycin complex 1 (mTORC1) signaling through two independent parallel pathways in the presence of DNA damage. / Cam, Maren; Bid, Hemant K.; Xiao, Linlin; Zambetti, Gerard P.; Houghton, Peter J.; Cam, Hakan.

In: Journal of Biological Chemistry, Vol. 289, No. 7, 14.02.2014, p. 4083-4094.

Research output: Contribution to journal › Article

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abstract = "Background: mTORC1 integrates cellular inputs and is often deregulated in cancer. Results: In response to DNA damage, p53/TAp63 and AKT regulate mTORC1 through two independent parallel pathways. Conclusion: DNA damage activates Akt, resulting in inhibition of S6K1, whereas Sestrin1/2 downstream of p53 and REDD1 downstream of p63 coordinate to suppress 4E-BP1. Significance: mTORC1-dependent 4EBP1 inhibition by DNA damage is abrogated in most human cancers.",

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10.1074/jbc.M113.530303