Unknown

Dataset Information

0

Alpha ketoglutarate levels, regulated by p53 and OGDH, determine autophagy and cell fate/apoptosis in response to Nutlin-3a.


ABSTRACT: Activated p53 can promote apoptosis or cell cycle arrest. Differences in energy metabolism can influence cell fate in response to activated p53. Nutlin-3a is a preclinical drug and small molecule activator of p53. Alpha-ketoglutarate (αKG) levels were reduced in cells sensitive to Nutlin-3a-induced apoptosis and increased in cells resistant to this apoptosis. Add-back of a cell-permeable αKG analog (DMKG) rescued cells from apoptosis in response to Nutlin-3a. OGDH is a component of the αKGDH complex that converts αKG to succinate. OGDH knockdown increased endogenous αKG levels and also rescued cells from Nutlin-3a-induced apoptosis. We previously showed reduced autophagy and ATG gene expression contributes to Nutlin-3a-induced apoptosis. DMKG and OGDH knockdown restored autophagy and ATG gene expression in Nutlin-3a-treated cells. These studies indicate αKG levels, regulated by p53 and OGDH, determine autophagy and apoptosis in response to Nutlin-3a.

SUBMITTER: Duan L 

PROVIDER: S-EPMC6370392 | BioStudies | 2019-01-01

REPOSITORIES: biostudies

Similar Datasets

1000-01-01 | S-EPMC4695109 | BioStudies
2015-01-01 | S-EPMC4595506 | BioStudies
1000-01-01 | S-EPMC6161407 | BioStudies
1000-01-01 | S-EPMC3185941 | BioStudies
2011-01-01 | S-EPMC3071734 | BioStudies
2008-01-01 | S-EPMC2674275 | BioStudies
1000-01-01 | S-EPMC2906304 | BioStudies
2010-01-01 | S-EPMC2840060 | BioStudies
2013-01-01 | S-EPMC3989211 | BioStudies
2008-01-01 | S-EPMC2440635 | BioStudies