ATF3 induction following DNA damage is regulated by distinct signaling pathways and over-expression of ATF3 protein suppresses cells growth
Abstract
Mammalian cells have a remarkable diverse repertoire of response to genotoxic stress that damage DNA. Cellular responses to DNA damaging agents will initially exhibit gene induction, which is regulated by complex mechanism(s) and probably involves multiple signaling pathways. In this paper, we demonstrate that induction of ATF3 protein, a member of the ATF/CREB family of transcription factors, by ionizing radiation (IR) requires normal cellular p53 function. In contrast, induction of ATF3 after UV radiation (UV) or Methyl methanesulphonate (MMS) is independent of p53 status. Induction of ATF3 by DNA damage is rapid, transient, and through a transcriptional mechanism. The ATF3 promoter is induced by UV and MMS, but not by IR. In addition, ATF3 promoter can be activated by MEKK1, an upstream activator of the ERK and JNK kinase pathway, but not induced following p53 expression. Those results indicate that regulation of ATF3 induction after DNA damage utilizes both the p53-dependent and -independent pathways, and may also involve MAP kinase signaling pathways. Using the tetracycline-inducible system (tet-off), we have found that over-expression of ATF3 protein moderately suppresses cell growth. Interestingly, over-expression of ATF3 protein is able to slow down progression of cells from G1 to S phase, indicating that ATF3 protein might play a negative role in the control of cell cycle progression.
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Quantitative proteomic analysis of protein expression changes conferred by asukamycin treatment in 231MFP cells showed many known p53 transcriptional targets upregulated, including GADD45A, GADD45B, ANKRD1, HMOX1, ATF3, PMAIP1, DDIT4, DNAJB9, and PLK2.
“quantitative proteomic analysis of protein expression changes conferred by asukamycin treatment in 231MFP cells showed many known p53 transcriptional targets upregulated in expression, including GADD45A, GADD45B, ANKRD1, HMOX1, ATF3, PMAIP1, DDIT4, DNAJB9, and PLK2 (Extended Data Figure 9) 31–37.”
From Manumycin polyketides act as molecular glues between UBR7 and P53 (2020) · cites this paper as [32]
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“Similarly, ATF3 has been reported to suppress or promote cell cycle progression (Fan et al., 2002; Lv et al., 2011).”
BackgroundSingle-cell transcriptomics for the assessment of cardiac disease
Miranda, A. M. A., Janbandhu, V., Maatz, H., Kanemaru, K., Cranley, J., Teichmann, S. A., Hübner, N., Schneider, M. D., Harvey, R. P., & Noseda, M. (2023) · Nature Reviews Cardiology · doi:10.1038/s41569-022-00805-7 · Cited by 117 · see citing works
Manumycin polyketides act as molecular glues between UBR7 and P53
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- Authors
- Fan, F., Jin, S., Amundson, S. A., Tong, T., Fan, W., Zhao, H., Zhu, X., Mazzacurati, L., Li, X., Petrik, K. L., Fornace, A. J., Rajasekaran, B., & Zhan, Q.
- Affiliations
- University of Pittsburgh (US)
- National Institutes of Health (US)
- Corresponding author
- Zhan, Qimin
- ORCID
- Venue
- Oncogene
- Published
- 2002-10-18
- Volume
- 21
- Issue
- 49
- Pages
- 7488-7496
- ISSN
- 0950-9232 (ISSN-L)
- 1476-5594
- OpenAlex
- W2316858638
- Cited by
- 198
- References
- 47
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 2 · 2023: 10 · 2022: 4 · 2021: 6 · 2020: 8 · 2019: 5 · 2018: 6 · 2017: 7 · 2016: 8 · 2015: 9 · 2014: 9 · 2013: 9 · 2012: 6
- FWCI
- 2.78
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Oncogene (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Keywords
- ATF3, DNA damage response, p53, ionizing radiation, ultraviolet radiation, methyl methanesulfonate, MEKK1, MAPK signaling, cell growth inhibition, G1/S transition, genotoxic stress
- MeSH terms
- Base Sequence, Cell Cycle, Cell Division, DNA Damage, Humans, Methyl Methanesulfonate, Promoter Regions, Genetic, Radiation, Ionizing, Transcription Factors, Transcription, Genetic, Tumor Cells, Cultured, Ultraviolet Rays, Transcriptional Activation, Gene Expression Regulation, Neoplastic, Tumor Suppressor Protein p53, DNA Primers, MAP Kinase Signaling System, Activating Transcription Factor 3
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