Upregulation of human autophagy-initiation kinase ULK1 by tumor suppressor p53 contributes to DNA-damage-induced cell death
Open accessAbstract
In yeast, activation of ATG1/ATG13 kinase complex initiates autophagy. This mechanism of autophagy initiation is conserved, as unc-51-like kinase 1 (ULK1) and unc-51-like kinase 2 (ULK2) are two mammalian functional homologues of ATG1 and form similar complex with mammalian ATG13. Here, we report that both ULK1 and ULK2 are transcriptional targets of tumor suppressor p53. In response to DNA damage, ULK1 and ULK2 are upregulated by p53. The upregulation of ULK1 (ULK2)/ATG13 complex by p53 is necessary for the sustained autophagy activity induced by DNA damage. In this context, elevated autophagy contributes to subsequent cell death. These findings suggest that ULK1 and ULK2 may mediate part of tumor suppression activity in mammalian cells and contribute to the efficacy of genotoxic chemotherapeutic drugs.
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ULK1 and ULK2, which encode autophagy-activating kinases, were thought to be regulated by p53, but their regulation by p53 is not supported by meta-analysis data.
“And, although ULK1 and ULK2, which encode autophagy-activating kinases, were thought to be regulated by p53,137 their regulation by p53 is not supported by meta-analysis data18 (Supplementary Table S2).”
From Census and evaluation of p53 target genes (2017) · cites this paper as [137]
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- Authors
- Gao, W., Shen, Z., Shang, L., & Wang, X.
- Affiliations
- Howard Hughes Medical Institute (US)
- Corresponding author
- Wang, X
- Venue
- Cell Death & Differentiation
- Published
- 2011-04-08
- Volume
- 18
- Issue
- 10
- Pages
- 1598-1607
- ISSN
- 1350-9047 (ISSN-L)
- 1476-5403
- PMC
- PMC3172118
- OpenAlex
- W2087510837
- Cited by
- 178
- References
- 40
- Citations by year
- 2026: 7 · 2025: 2 · 2024: 5 · 2023: 5 · 2022: 13 · 2021: 13 · 2020: 16 · 2019: 12 · 2018: 9 · 2017: 15 · 2016: 15 · 2015: 12 · 2014: 17 · 2013: 15 · 2012: 18
- FWCI
- 12.96
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc-nd
- www.springer.com/tdm (unspecified)
- Locations
- Cell Death and Differentiation (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- Welch Foundation
- Topics
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Keywords
- ULK1, ULK2, p53, autophagy initiation, ATG13, DNA damage, DNA damage-induced cell death, transcriptional regulation, tumor suppression, genotoxic chemotherapy
- MeSH terms
- Autophagy-Related Proteins, Autophagy-Related Protein-1 Homolog, Autophagy, DNA Damage, Humans, Polymerase Chain Reaction, Tumor Suppressor Protein p53, Cell Death, Protein Serine-Threonine Kinases, Electrophoretic Mobility Shift Assay, RNA Interference, Intracellular Signaling Peptides and Proteins, Adaptor Proteins, Signal Transducing
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