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dc.contributor.authorPatel, VA
dc.contributor.authorMassenburg, D
dc.contributor.authorVujicic, S
dc.contributor.authorFeng, L
dc.contributor.authorTang, M
dc.contributor.authorLitbarg, N
dc.contributor.authorAntoni, A
dc.contributor.authorRauch, J
dc.contributor.authorLieberthal, W
dc.contributor.authorLevine, JS
dc.date.accessioned2016-05-12T20:37:29Z
dc.date.available2016-11-13T10:30:04Z
dc.date.issued2015-09-11
dc.identifier.bibliographicCitationPatel, V. A., Massenburg, D., Vujicic, S., Feng, L., Tang, M., Litbarg, N., Antoni, A., Rauch, J., Lieberthal, W. and Levine, J. S. Apoptotic cells activate AMP-activated protein kinase (AMPK) and inhibit epithelial cell growth without change in intracellular energy stores. Journal of Biological Chemistry. 2015. 290(37): 22352-22369. DOI: 10.1074/jbc.M115.667345.en_US
dc.identifier.issn0021-9258
dc.identifier.urihttp://hdl.handle.net/10027/20624
dc.descriptionThis is the author’s version of a work that was accepted for publication in Journal of Biological Chemistry. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Journal of Biological Chemistry. 2015. 290(37): 22352-22369. DOI: 10.1074/jbc.M115.667345.en_US
dc.description.abstractApoptosis plays an indispensable role in the maintenance and development of tissues. We have shown that receptor-mediated recognition of apoptotic target cells by viable kidney proximal tubular epithelial cells (PTECs) inhibits the proliferation and survival of PTECs. Here, we examined the effect of apoptotic targets on PTEC cell growth (cell size during G1 phase of the cell cycle). Using a cell culture model, we show that apoptotic cells potently activate AMP-activated protein kinase (AMPK), a highly sensitive sensor of intracellular energy stores. AMPK activation leads to decreased activity of its downstream target, ribosomal protein p70 S6 kinase (p70S6K), and concomitant inhibition of cell growth. Importantly, these events occur without detectable change in intracellular levels of AMP, ADP, or ATP. Inhibition of AMPK, either pharmacologically by compound C or molecularly by shRNA, diminishes the effects of apoptotic targets and largely restores p70S6K activity and cell size to normal levels. Apoptotic targets also inhibit Akt, a second signaling pathway regulating cell growth. Expression of a constitutively active Akt construct partially relieved cell growth inhibition but was less effective than inhibition of AMPK. Inhibition of cell growth by apoptotic targets is dependent on physical interaction between apoptotic targets and PTECs but independent of phagocytosis. We conclude that receptor-mediated recognition of apoptotic targets mimics the effects of intracellular energy depletion, activating AMPK and inhibiting cell growth. By acting as sentinels of environmental change, apoptotic death may enable nearby viable cells, especially nonmigratory epithelial cells, to monitor and adapt to local stresses.en_US
dc.description.sponsorshipGrant Support MOP-67101/Canadian Institutes of Health Research/Canada MOP-97916/Canadian Institutes of Health Research/Canada S10RR024516/RR/NCRR NIH HHS/United Statesen_US
dc.publisherAmerican Society for Biochemistry and Molecular Biologyen_US
dc.subjectADPen_US
dc.subjectAMPen_US
dc.subjectAMP-activated kinase (AMPK)en_US
dc.subjectATPen_US
dc.subjectAkt PKBen_US
dc.subjectapoptosisen_US
dc.subjectcell growthen_US
dc.subjectepithelial cellen_US
dc.subjectinnate immunityen_US
dc.subjectkidneyen_US
dc.titleApoptotic cells activate AMP-activated protein kinase (AMPK) and inhibit epithelial cell growth without change in intracellular energy stores.en_US
dc.typeArticleen_US


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