ArticleOncogene2005
Knockdown of p53 levels in human keratinocytes accelerates Mcl-1 and Bcl-x(L) reduction thereby enhancing UV-light induced apoptosis.
Article in Oncogene, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
15 citing papers in PubMed, 48 citations in OpenAlex.
- Interferon alpha promotes caspase-8 dependent ultraviolet light-mediated keratinocyte apoptosis via interferon regulatory factor 1.Frontiers in immunology · 2024Article
- Computational modeling of DLBCL predicts response to BH3-mimetics.NPJ systems biology and applications · 2023Article
- Rethinking Causation for Data-intensive Biology: Constraints, Cancellations, and Quantized Organisms: Causality in complex organisms is sculpted by constraints rather than instigators, with outcomes perhaps better described by quantized patterns than rectilinear pathways.BioEssays : news and reviews in molecular, cellular and developmental biology · 2020Article
- Exogenous p53 and ASPP2 expression enhances rAdV-TK/ GCV-induced death in hepatocellular carcinoma cells lacking functional p53.Oncotarget · 2016Article
- Cordyceps militaris extract protects human dermal fibroblasts against oxidative stress-induced apoptosis and premature senescence.Nutrients · 2014Article
- Putative role of HIF transcriptional activity in melanocytes and melanoma biology.Dermato-endocrinology · 2013Review
- P53 in human melanoma fails to regulate target genes associated with apoptosis and the cell cycle and may contribute to proliferation.BMC cancer · 2011Article
- Chromatin structure following UV-induced DNA damage-repair or death?International journal of molecular sciences · 2011Review
- Potent inhibition of rhabdoid tumor cells by combination of flavopiridol and 4OH-tamoxifen.BMC cancer · 2010Article
- Regulation of serum response factor activity and smooth muscle cell apoptosis by chromodomain helicase DNA-binding protein 8.American journal of physiology. Cell physiology · 2010Article
- MMP-13 plays a role in keratinocyte migration, angiogenesis, and contraction in mouse skin wound healing.The American journal of pathology · 2009Article
- Mcl-1 functions as major epidermal survival protein required for proper keratinocyte differentiation.The Journal of investigative dermatology · 2009Article
- A new paradigm for the role of aging in the development of skin cancer.The Journal of investigative dermatology · 2009Article
- RPA and ATR link transcriptional stress to p53.Proceedings of the National Academy of Sciences of the United States of America · 2007Article
- Keratinocyte apoptosis in epidermal development and disease.The Journal of investigative dermatology · 2006Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
Ultraviolet (UV) light exposure is a common cause of epithelial-derived skin cancers, and the epidermal response to UV-light has been extensively studied using both mouse models and cultured human keratinocytes (KCs). Elimination of cells with UV-induced DNA damage via apoptosis provides a powerful mechanism to minimize retention or expansion of genetically abnormal cells. This cell editing function has largely been ascribed to the biological role of the p53 tumor suppressor gene, as mutations or deletions involving p53 have been linked to skin cancer development. Rather than introducing mutations, or using cells with complete loss of wild-type p53, we used an siRNA-based approach to knockdown, but not eliminate, p53 levels in primary cultures of human KCs followed by UV-irradiation. Surprisingly, when p53 levels were reduced by 50-80% the apoptosis induced by exposure to UV-light was accelerated and markedly enhanced (two- to three- fold) compared to control siRNA treated KCs. The p53 siRNA treated KCs were characterized by elevated E2F-1 levels accompanied by accelerated elimination of the Mcl-1 and Bcl-x(L) antiapoptotic proteins, as well as enhanced Bax oligomerization. Forced overexpression of either Mcl-1 or Bcl-x(L) reduced the UV-light enhanced apoptotic response in p53 siRNA treated KCs. We conclude that p53 not only can provide proapoptotic signals but also regulates a survival pathway influencing Mcl-1 and Bcl-x(L) levels. This overlooked survival function of p53 may explain previous paradoxical responses noted by investigators using p53 heterozygous and knockout mouse models, and opens up the possibility that not all liaisons within the cell involving p53 necessarily represent fatal attractions.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.