p53 activates the PANK1/ miRNA-107 gene leading to downregulation of CDK6 and p130 cell cycle proteins
Open accessAbstract
The tumor suppressor p53 is a central regulator of cell-cycle arrest and apoptosis by acting as a transcription factor to regulate numerous genes. We identified all human p53-regulated mRNAs by microarray analyses and searched for protein-coding genes which contain intronic miRNAs. Among others, this analysis yielded the panthothenate kinase 1 (PANK1) gene and its intronic miRNA-107. We showed that miRNA-107 and PANK1 are coregulated by p53 in different cell systems. The PANK1 protein, which catalyzes the rate-limiting step of coenzyme A biosynthesis, is also upregulated by p53. We observed that p53 directly activates PANK1 and miRNA-107 transcription through a binding site in the PANK1 promoter. Furthermore, p53 is recruited to the PANK1 promoter after DNA damage. In order to get more insight into miRNA-107 function we investigated its potential target genes. Cell-cycle regulators are significantly enriched among predicted miRNA-107 targets. We found miRNA-107-dependent regulation of two important regulators of G(1)/S progression, CDK6 and the RB-related 2 gene RBL2 (p130). CDK6 and p130 proteins are downregulated upon miRNA-107 expression. Our results uncover a novel miRNA-dependent signaling pathway which leads to downregulation of cell cycle proteins in the absence of transcriptional repression.
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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 [199]
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- Authors
- Böhlig, L., Friedrich, M., & Engeland, K.
- Affiliations
- Leipzig University (DE)
- Corresponding author
- Engeland, Kurt
- Venue
- Nucleic Acids Research
- Publisher
- Oxford University Press (OUP)
- Published
- 2010-09-10
- Volume
- 39
- Issue
- 2
- Pages
- 440-453
- ISSN
- 0305-1048 (ISSN-L)
- 1362-4962
- PMC
- PMC3025554
- OpenAlex
- W2164073093
- Cited by
- 85
- References
- 68
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 6 · 2023: 1 · 2022: 5 · 2021: 3 · 2020: 5 · 2019: 3 · 2018: 5 · 2017: 7 · 2016: 5 · 2015: 7 · 2014: 10 · 2013: 6 · 2012: 9
- FWCI
- 3.63
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Nucleic Acids Research (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Funders
- Sächsisches Staatsministerium für Wissenschaft und Kunst
- Topics
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer-related molecular mechanisms research
- Keywords
- p53, intronic microRNA, coenzyme A biosynthesis, CDK6, p130, RBL2, cell cycle regulation, DNA damage response, transcriptional regulation, tumor suppressor
- MeSH terms
- Cell Cycle, Cell Line, DNA Damage, Gene Expression Regulation, Humans, Introns, Promoter Regions, Genetic, Protein Biosynthesis, Transcriptional Activation, Down-Regulation, Tumor Suppressor Protein p53, Phosphotransferases (Alcohol Group Acceptor), Cell Cycle Proteins, Computational Biology, MicroRNAs, Retinoblastoma-Like Protein p130, Cyclin-Dependent Kinase 6, Genetic Loci
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