The first 30 years of p53: growing ever more complex

By Arnold J. Levine, Moshe Oren. Nature Reviews. Cancer, 2009

1,883 citations recorded by the source corpus.

Thirty years ago p53 was discovered as a cellular partner of simian virus 40 large T-antigen, the oncoprotein of this tumour virus. The first decade of p53 research saw the cloning of p53 DNA and the realization that p53 is not an oncogene but a tumour suppressor that is very frequently mutated in human cancer. In the second decade of research, the function of p53 was uncovered: it is a transcription factor induced by stress, which can promote cell cycle arrest, apoptosis and senescence. In the third decade after its discovery new functions of this protein were revealed, including the regulation of metabolic pathways and cytokines that are required for embryo implantation. The fourth decade of research may see new p53-based drugs to treat cancer. What is next is anybody's guess.

Subfields: Biotechnology, Molecular Biology, Oncology

View Paper: https://www.semanticscholar.org/paper/a0ffe364846cad6e1e49c506b26bff3ce88bdda0

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Citations in the corpus

Mutant p53: one name, many proteins. (2012, background): “It was soon recognized that these early experiments demonstrating that p53 overexpression could transform cells and promote in vivo tumor growth were actually performed with mutated versions of p53 that had been isolated from tumor cells (Hinds et al. 1989, 1990; Levine and Oren 2009).”
Mitochondrial reactive oxygen species and cancer (2014, background): “The most common of them, the tumor suppressor p53, known as ‘the guardian of the genome’ is lost or mutated in approximately 50% of cancers [72].”
Hydrogen peroxide sensing, signaling and regulation of transcription factors (2014, background): “TP53 (Tumor protein TP53, TTP53, Li-Fraumeni syndrome 1) has been studied for nearly three decades, and is best known for its potent ability to be a tumor suppressor [98].”
Revealing strengths and weaknesses of methods for gene network inference (2010, background): “For example, it took more than a decade from the discovery of the well known tumor suppressor gene p53 to determine that it formed a regulatory feedback loop with the protein MDM2, its key regulator (1).”
Genomic features of response to combination immunotherapy in patients with advanced non-small cell lung cancer (2018, background): “Notably, TP53mutations were also associated with increased mutation burden in both the cohort of combination immunotherapy NSCLCs and TCGA NSCLCs (Figures S3C–S3F and Table S4).”
Aging, Cellular Senescence, and Cancer (2012, background): “Both pathways are complex; each has multiple upstream regulators, downstream effectors, and modifying side branches (69, 70).”
Cell-free nucleic acids as biomarkers in cancer patients (2011, background): “Several therapeutic agents in clinical trials target the KRAS, BRAF, EGFR or p53 pathway”
Awakening guardian angels: drugging the p53 pathway (2009, background): “Consequently, the challenge has been — as highlighted by Levine and Ore”
Mechanisms of Cellular Senescence: Cell Cycle Arrest and Senescence Associated Secretory Phenotype (2021, background): “Both these pathways are complex as they involve many upstream regulators and downstream effectors along with varying side branches (Chau and Wang, 2003; Levine and Oren, 2009).”
DNA replication stress as a hallmark of cancer. (2015, background): “In somatic cells, p53 protein levels increase in response to DNA damage, leading to activation of target genes that induce cell cycle arrest, senescence, or apoptosis (54).”
Mutations in the p53 Tumor Suppressor Gene: Important Milestones at the Various Steps of Tumorigenesis. (2011, background): “Despite the huge diversity in the genes implicated in tumorigenesis, the p53 transcription factor (encoded by the human gene TP53) stands out as a key tumor suppressor and a master regulator of various signaling pathways involved in this process.(4,5) The many roles of p53 as a tumor suppressor incl”