DRAM, a p53-Induced Modulator of Autophagy, Is Critical for Apoptosis
Open accessAbstract
Inactivation of cell death is a major step in tumor development, and p53, a tumor suppressor frequently mutated in cancer, is a critical mediator of cell death. While a role for p53 in apoptosis is well established, direct links to other pathways controlling cell death are unknown. Here we describe DRAM (damage-regulated autophagy modulator), a p53 target gene encoding a lysosomal protein that induces macroautophagy, as an effector of p53-mediated death. We show that p53 induces autophagy in a DRAM-dependent manner and, while overexpression of DRAM alone causes minimal cell death, DRAM is essential for p53-mediated apoptosis. Moreover, analysis of DRAM in primary tumors revealed frequent decreased expression often accompanied by retention of wild-type p53. Collectively therefore, these studies not only report a stress-induced regulator of autophagy but also highlight the relationship of DRAM and autophagy to p53 function and damage-induced programmed cell death.
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Detection of DRAM1 RNA is very easy by qRT-PCR during autophagy; however, detection of the DRAM1 protein is very difficult because of its small size and hydrophobicity.
“Detection of DRAM1 RNA is very easy by qRT-PCR during autophagy; 438,439 however, detection of the DRAM1 protein is very difficult because of its small size and hydrophobicity, which makes generation of specific antibodies a complicated process, and in general these have very low sensitivity.”
From Guidelines for the use and interpretation of assays for monitoring autophagy (2012) · cites this paper as [438]
The citation is attached to the RNA-detection clause. The Results report measuring DRAM mRNA by real-time quantitative RT-PCR after p53 induction, but do not establish that detection is “very easy” or specifically describe qRT-PCR detection during autophagy. The later protein-detection clause follows the citation and is not assessed here. (LLM, conf=0.78)
Experimental — accuracy not yet measuredDRAM1 is a gene induced by activated TP53/p53 in response to different types of cellular stress, including DNA damage.
“DRAM1 (damage-regulated autophagic modulator 1) is a gene induced by activated TP53/p53 in response to different types of cellular stress, including DNA damage.438,439”
From Guidelines for the use and interpretation of assays for monitoring autophagy (2012) · cites this paper as [438]
The p53 target gene DRAM1 encodes a lysosomal membrane protein that is required for the induction of autophagy by p53.
“The p53 target gene DRAM1 encodes a lysosomal membrane protein that is required for the induction of autophagy by p53.209”
From Census and evaluation of p53 target genes (2017) · cites this paper as [209]
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“In addition, protein 53 can also result in inducement of cell cycle arrest at G2/M stage of the cell cycle by transcriptionally activating protein 21, the inhibitor of cyclin-dependent kinases [98, 99], and may induce autophagy in a DRAM (damage-regulated autophagy modulator) dependent manner [100].”
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- Authors
- Crighton, D., Wilkinson, S., O'Prey, J., Syed, N., Smith, P., Harrison, P. R., Gasco, M., Garrone, O., Crook, T., & Ryan, K. M.
- Affiliations
- Cancer Research UK (GB)
- Institute of Cancer Research (GB)
- Azienda Sanitaria Ospedaliera S.Croce e Carle Cuneo (IT)
- Corresponding author
- Ryan, Kevin M.
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2006-07
- Volume
- 126
- Issue
- 1
- Pages
- 121-134
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W2150027419
- Cited by
- 1,380
- References
- 43
- Citations by year
- 2026: 28 · 2025: 36 · 2024: 49 · 2023: 41 · 2022: 59 · 2021: 69 · 2020: 91 · 2019: 66 · 2018: 75 · 2017: 61 · 2016: 68 · 2015: 80 · 2014: 88 · 2013: 117 · 2012: 107
- FWCI
- 46.81
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 2573 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- ENLIGHTEN (Jurnal Bimbingan dan Konseling Islam) (submittedVersion)
- 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
- DRAM, p53, autophagy, apoptosis, macroautophagy, lysosomal proteins, p53 target genes, programmed cell death, tumor suppressor, primary tumor
- MeSH terms
- Amino Acid Sequence, Animals, Autophagy, Base Sequence, Binding Sites, Carcinoma, Cell Line, Cell Transformation, Neoplastic, DNA Damage, Humans, Lysosomes, Membrane Proteins, Molecular Sequence Data, Protein Binding, Proteins, Down-Regulation, Tumor Suppressor Protein p53, Conserved Sequence, Apoptosis, Oxidative Stress, Cell Line, Tumor
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