p53-dependent regulation of metabolic function through transcriptional activation of pantothenate kinase-1 gene
Open accessAbstract
It is well established that the p53 tumor suppressor plays a crucial role in controlling cell proliferation and apoptosis upon various types of stress. There is increasing evidence showing that p53 is also critically involved in various metabolic pathways, both in tumor and normal cells. Here, we have identified a novel p53 metabolic target pantothenate kinase-1 (PANK1) via ChIP-on-chip. PanK1 catalyzes the rate-limiting step for CoA synthesis and, therefore, controls intracellular CoA content; Pank1-knockout mice exhibit defect in β-oxidation and gluconeogenesis in the liver after starvation due to insufficient CoA levels. We demonstrated that PANK1 gene is a direct transcriptional target of p53. Although DNA damage-induced p53 upregulates PanK1 expression, depletion of PanK1 expression does not affect p53-dependent growth arrest or apoptosis. Interestingly, upon glucose starvation, PanK1 expression is significantly reduced in HCT116 p53 (-/-) but not in HCT116 p53 (+/+) cells, suggesting that p53 is required to maintain PanK1 expression under metabolic stress conditions. Moreover, by using p53-mutant mice, we observed that, similar to the case in Pank1-knockout mice, gluconeogenesis is partially impaired in p53-null mice. Together, our findings show that p53 plays an important role in regulating energy homeostasis through transcriptional control of PANK1, independent of its canonical functions in apoptosis and cell cycle arrest.
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PANK1 is a p53 target, which encodes for a key regulatory enzyme in the biosynthesis of coenzyme A.
“PANK1 is a p53 target, which encodes for a key regulatory enzyme in the biosynthesis of coenzyme A.199, 200”
From Census and evaluation of p53 target genes (2017) · cites this paper as [200]
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- Authors
- Wang, S.-J., Yu, G., Jiang, L., Li, T., Lin, Q., Tang, Y., & Gu, W.
- Affiliations
- Columbia University (US)
- Albany Medical College (US)
- Corresponding author
- Tang, Yi
- Gu, Wei
- Venue
- Cell Cycle
- Publisher
- Informa UK Limited
- Published
- 2013-03
- Volume
- 12
- Issue
- 5
- Pages
- 753-761
- ISSN
- 1538-4101 (ISSN-L)
- 1551-4005
- PMC
- PMC3610723
- OpenAlex
- W2009045169
- Cited by
- 54
- References
- 28
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 3 · 2023: 5 · 2022: 8 · 2021: 5 · 2020: 3 · 2019: 5 · 2018: 8 · 2017: 2 · 2016: 3 · 2015: 3 · 2014: 2 · 2013: 1
- FWCI
- 1.61
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Cell Cycle (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (2r01ca085533-16)
- National Cancer Institute (R01-CA085533, CA172023, P01CA097403, CA-09503, CA080058, T32 CA 09503, P01CA080058, T32CA009503, R01CA172023)
- Topics
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Lipids, and Metabolism
- Keywords
- p53, transcriptional regulation, coenzyme A synthesis, metabolic stress, glucose deprivation, gluconeogenesis, energy homeostasis, DNA damage response, p53-null mice, HCT116 cells
- MeSH terms
- Animals, Base Sequence, DNA Damage, Gluconeogenesis, Humans, Molecular Sequence Data, Transcriptional Activation, Gene Expression Regulation, Neoplastic, Tumor Suppressor Protein p53, Apoptosis, Phosphotransferases (Alcohol Group Acceptor), HCT116 Cells, Mice
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