p53 Pathway
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Get Print CopyAutophagy
Induction
Autophagy
Induction
Translation
Inhibition
Translation
Inhibition
Apoptosis
Apoptosis
p53
Degradation
p53
Degradation
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Cell Cycle
Arrest/DNA
Repair
Cell Cycle
Arrest/DNA
Repair
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Proteins
Proteins
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Overview of p53 Pathways
p53 is a transcription factor that is well known for its key role as a tumor suppressor protein. Mutations in the p53 gene are one of the most frequent genomic events accompanying oncogenic transformation. Because of its critical cellular roles, p53 expression is tightly regulated post-translationally. Under basal conditions, p53 protein levels are negatively regulated by E3 ubiquitin ligases, including MDM2, which is the most widely studied. These E3 ligases promote the ubiquitination and subsequent proteasome-dependent degradation of p53. In response to stress stimuli, including DNA damage, nucleolar stress, metabolic stress, and oncogenic stress, p53 protein levels become stabilized. Once stable, p53 binds DNA as a homotetramer and activates the transcription of genes involved in many cellular processes that inhibit cancer progression, including apoptosis, cell cycle arrest, and senescence. p53 can also promote apoptosis independently of its transcriptional activity through interactions with Bcl-2 family proteins in the cytoplasm.
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