REDD1, a Developmentally Regulated Transcriptional Target of p63 and p53, Links p63 to Regulation of Reactive Oxygen Species
Open accessAbstract
We identified REDD1 as a novel transcriptional target of p53 induced following DNA damage. During embryogenesis, REDD1 expression mirrors the tissue-specific pattern of the p53 family member p63, and TP63 null embryos show virtually no expression of REDD1, which is restored in mouse embryo fibroblasts following p63 expression. In differentiating primary keratinocytes, TP63 and REDD1 expression are coordinately downregulated, and ectopic expression of either gene inhibits in vitro differentiation. REDD1 appears to function in the regulation of reactive oxygen species (ROS); we show that TP63 null fibroblasts have decreased ROS levels and reduced sensitivity to oxidative stress, which are both increased following ectopic expression of either TP63 or REDD1. Thus, REDD1 encodes a shared transcriptional target that implicates ROS in the p53-dependent DNA damage response and in p63-mediated regulation of epithelial differentiation.
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Redd1 is a new stress-induced protein and a negative regulator of mTOR through the TSC1/TSC2 complex.
“Redd1 is a new stress-induced protein and is known as a negative regulator of mTOR through TSC1/TSC2 complex [106–115].”
From PKR, the double stranded RNA‐dependent protein kinase as a critical target in Alzheimer's disease (2009) · cites this paper as [106]
The Results report that REDD1 protein increases after ionizing radiation or MMS treatment and identify REDD1 as the stress-induced gene RTP801 (page not provided). The cited paper does not establish that REDD1 negatively regulates mTOR through the TSC1/TSC2 complex; its Discussion instead focuses on regulation of reactive oxygen species. (LLM, conf=0.88)
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- Authors
- Ellisen, L. W., Ramsayer, K. D., Johannessen, C. M., Yang, A., Beppu, H., Minda, K., Oliner, J. D., McKeon, F., & Haber, D. A.
- Affiliations
- Harvard University (US)
- Affymetrix (United States) (US)
- Corresponding author
- Haber, Daniel A
- Venue
- Molecular Cell
- Publisher
- Elsevier BV
- Published
- 2002-11
- Volume
- 10
- Issue
- 5
- Pages
- 995-1005
- ISSN
- 1097-2765 (ISSN-L)
- OpenAlex
- W1978510296
- Cited by
- 474
- References
- 4
- Citations by year
- 2026: 12 · 2025: 20 · 2024: 13 · 2023: 19 · 2022: 28 · 2021: 34 · 2020: 17 · 2019: 24 · 2018: 20 · 2017: 11 · 2016: 21 · 2015: 19 · 2014: 37 · 2013: 19 · 2012: 32
- FWCI
- 4.89
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Molecular Cell (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5k08ca082831-02)
- National Cancer Institute (CA 84066, CA82831, R01CA122589, R01CA084066)
- Topics
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Keywords
- REDD1, p63, p53, transcription factor target genes, reactive oxygen species, DNA damage response, embryonic development, keratinocyte differentiation, epithelial differentiation, oxidative stress, mouse embryonic fibroblasts
- MeSH terms
- Adenoviridae, Amino Acid Sequence, Animals, Base Sequence, beta-Galactosidase, Cell Differentiation, Cloning, Molecular, DNA-Binding Proteins, Epithelial Cells, Fibroblasts, Gene Expression Regulation, Humans, Membrane Proteins, Microscopy, Fluorescence, Molecular Sequence Data, Phosphoproteins, Precipitin Tests, Promoter Regions, Genetic, RNA, Messenger, Transcription Factors, Transcription, Genetic, Ultraviolet Rays, Xenopus, Blotting, Northern, Blotting, Western, Transcriptional Activation, Trans-Activators, Down-Regulation, Keratinocytes, Up-Regulation, Genes, Tumor Suppressor, Tumor Suppressor Protein p53, Conserved Sequence, Reactive Oxygen Species, Sequence Homology, Amino Acid, In Situ Hybridization, Oxidative Stress, Evolution, Molecular, Protein Isoforms, Oligonucleotide Array Sequence Analysis, Tumor Suppressor Proteins, Xenopus Proteins, Mice
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