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Cytoplasmic functions of the tumour suppressor p53

TLDR
An emerging area of research unravels additional activities of p53 in the cytoplasm, where it triggers apoptosis and inhibits autophagy, which contribute to the mission of p 53 as a tumour suppressor.
Abstract
The principal tumour-suppressor protein, p53, accumulates in cells in response to DNA damage, oncogene activation and other stresses. It acts as a nuclear transcription factor that transactivates genes involved in apoptosis, cell cycle regulation and numerous other processes. An emerging area of research unravels additional activities of p53 in the cytoplasm, where it triggers apoptosis and inhibits autophagy. These previously unknown functions contribute to the mission of p53 as a tumour suppressor.

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Journal ArticleDOI

Autophagy and the Integrated Stress Response

TL;DR: Autophagy is a cell biological process that is a central component of the integrated stress response and can be integrated with other cellular stress responses through parallel stimulation of autophagy and other stress responses by specific stress stimuli.
Journal ArticleDOI

Control of apoptosis by the BCL-2 protein family: implications for physiology and therapy

TL;DR: The biochemical, structural and genetic studies that have clarified how the interplay between members of the BCL-2 family on mitochondria sets the apoptotic threshold are discussed, illuminating the physiological control of apoptosis, the pathological consequences of its dysregulation and the promising search for novel cancer therapies that target the BCA2 protein family.
Journal ArticleDOI

The first 30 years of p53: growing ever more complex

TL;DR: Thirty years ago p53 was discovered as a cellular partner of simian virus 40 large T-antigen, the oncoprotein of this tumour virus, and new functions of this protein were revealed, including the regulation of metabolic pathways and cytokines that are required for embryo implantation.
Journal ArticleDOI

Molecular Genetics of Colorectal Cancer

TL;DR: In this article, a review of gene mutations in colorectal cancer is presented, focusing on the nature and significance of individual and collective genetic and epigenetic defects in CRC.
Journal ArticleDOI

Crosstalk between apoptosis, necrosis and autophagy.

TL;DR: The recent literature that highlights the intricate interplay between apoptosis, necrosis and autophagy is reviewed, focusing on the relevance and impact of this crosstalk in normal development and in pathology.
References
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Journal ArticleDOI

Autophagy in the Pathogenesis of Disease

TL;DR: This Review summarizes recent advances in understanding the physiological functions of autophagy and its possible roles in the causation and prevention of human diseases.
Journal ArticleDOI

Mitochondrial Membrane Permeabilization in Cell Death

TL;DR: Once MMP has been induced, it causes the release of catabolic hydrolases and activators of such enzymes (including those of caspases) from mitochondria, meaning that mitochondria coordinate the late stage of cellular demise.
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Role of autophagy in cancer

TL;DR: Evidence suggests that autophagy provides a protective function to limit tumour necrosis and inflammation, and to mitigate genome damage in tumour cells in response to metabolic stress.
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Direct activation of Bax by p53 mediates mitochondrial membrane permeabilization and apoptosis.

TL;DR: It is proposed that when p53 accumulates in the cytosol, it can function analogously to the BH3-only subset of proapoptotic Bcl-2proteins to activate Bax and trigger apoptosis.
Journal ArticleDOI

Transcriptional control of human p53-regulated genes

TL;DR: The most comprehensive list so far of human p53-regulated genes and their experimentally validated, functional binding sites that confer p53 regulation is presented.
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