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Yeast As a Chassis for Developing Functional Assays to Study Human P53
Published on: August 4, 2019
Decision Making by p53: Life versus Death
Lingyan Jiang1, M Saeed Sheikh, Ying Huang
1Department of Pharmacology, State University of New York, Upstate Medical University, Syracuse, New York.
Abstract:
Cellular response to DNA damage is multifacted in nature and involves a complex signaling network in which p53 functions as a "molecular node" for converging signals. p53 has been implicated in a variety of cellular processes primarily functioning as a transcription factor and also in a transcription-independent manner. It is rapidly activated following DNA damage with phosphorylation as one of the initial signals. Cellular context as well as the type and severity of DNA damage determine p53 activation code, and its activities are regulated predominantly through protein degradation, post-translational modification and interactions with various cellular co-factors. These events are crucial in decision making by p53 as it has the ability to receive, assess and integrate different signals and route them accordingly to induce cell death or promote cell survival. In this decision making process, its transcriptional role to activate a specific subset of target genes linked to inducing cell cycle arrest or apoptosis is critical that is further fine-tuned by its transcription-independent function. This article reviews the current state of knowledge about the role of p53 in determining the fate of cells that have incurred DNA damage.
Insights
The tumor suppressor p53 protein acts as a central regulator in the cellular DNA damage response. It integrates signals to decide cell fate, promoting survival or apoptosis.
Area of Science:
- Molecular Biology
- Cell Biology
- Genetics
Background:
- The tumor suppressor protein p53 is a critical component of the cellular signaling network that responds to DNA damage.
- p53 functions as a transcription factor and also in a transcription-independent manner, playing a key role in cellular processes.
- Its activation is rapid following DNA damage, with phosphorylation being an initial signaling event.
Purpose of the Study:
- To review the current understanding of p53's role in cellular decision-making following DNA damage.
- To elucidate how p53 integrates diverse cellular signals to determine cell fate.
- To highlight the transcriptional and transcription-independent functions of p53 in DNA damage response.
Main Methods:
- Literature review of studies on p53 function in DNA damage response.
- Analysis of signaling pathways involving p53 activation and regulation.
- Examination of p53's role in cell cycle arrest, apoptosis, and cell survival.
Main Results:
- p53 acts as a molecular node, integrating signals from DNA damage.
- Cellular context and damage type/severity dictate p53 activation and function.
- p53's activities are regulated by protein degradation, post-translational modifications, and cofactor interactions.
- p53's transcriptional role in activating target genes for cell cycle arrest or apoptosis is critical.
- Transcription-independent functions further fine-tune p53's role in cell fate determination.
Conclusions:
- p53 plays a pivotal role in determining the fate of cells experiencing DNA damage.
- Its ability to assess and integrate signals allows it to direct cells towards survival or death.
- Understanding p53 regulation is crucial for comprehending cellular responses to genotoxic stress.
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