KRAB-type zinc-finger proteins PITA and PISA specifically regulate p53-dependent glycolysis and mitochondrial respiration

Cell Research
Shan WangLingqiang Zhang

Abstract

Few p53 regulators participate in selective control of p53-mediated cellular metabolism. How p53-mediated aerobic and glycolytic pathways are negatively regulated remains largely unclear. Here, we identified two KRAB-type zinc-finger proteins, PITA (p53 inhibitor of TIGAR activation) and PISA (p53 inhibitor of SCO2 activation), as selective regulators of p53 in metabolic control. PITA and PISA interact with p53 and specifically suppress transcription of the glycolysis regulator TIGAR and the oxidation phosphorylation regulator SCO2, respectively. Importantly, PITA transgenic mice exhibited increased 6-phosphofructokinase 1 (PFK1) activity and an elevated glycolytic rate, whereas PISA transgenic mice had decreased cytochrome c oxidase activity and reduced mitochondrial respiration. In response to glucose starvation, PITA dissociates from p53, resulting in activation of p53 and induction of TIGAR, which inhibited aerobic glycolysis. Prolonged starvation leads to PISA dissociation from p53 and induction of SCO2 and p53-promoted mitochondrial respiration. The dynamic regulation of PITA and PISA upon metabolic stress is dependent on ATM kinase-mediated phosphorylation of PITA and PISA. Furthermore, in human colorectal cancers, the e...Continue Reading

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Citations

Apr 5, 2019·Oncology Letters·Lin Jin, Yanhong Zhou
Apr 21, 2021·Cell Cycle·Danilo CucchiSarah A Martin
Apr 27, 2021·Antioxidants & Redox Signaling·Masuko Ushio-FukaiTohru Fukai
Jun 3, 2021·Genes & Development·Jiexi LiRonald A DePinho
May 18, 2021·Atherosclerosis·Zhen-Wang ZhaoChao-Ke Tang
Aug 10, 2021·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Payel MondalChandrima Das
Dec 28, 2021·Diabetes·Nehaben A GujaratiSandeep K Mallipattu

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Datasets Mentioned

BETA
SUB3220387

Methods Mentioned

BETA
PISA
PCR
immunoprecipitation
pull-down
PITA
co-immunoprecipitation
ChIP
electrophoresis
ChIP-seq
transgenic

Software Mentioned

Circos
DAVID
PITA
GraphPad Prism
Scansite
Cluster
RESM
Image Pro plus
SPSS
PISA

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