p53regulated

p53regulated refers to genes and gene networks whose expression is controlled by the tumor suppressor protein p53. In response to cellular stress such as DNA damage, oncogenic signals, or hypoxia, p53 acts as a transcription factor to activate or repress a broad set of target genes, guiding outcomes that preserve genomic integrity or promote cell death when damage is irreparable.

Mechanism: p53 binds to DNA as a tetramer at specific response elements and recruits transcriptional co-activators like p300/CBP. Its activity is regulated by post-translational modifications, including phosphorylation and acetylation, and by ubiquitination through MDM2, which forms a negative feedback loop. p53 can also repress transcription indirectly via interactions with other factors or chromatin modifiers.

Examples of p53-regulated genes and pathways: In cell cycle control, p53 induces CDKN1A (p21), leading to G1/S arrest. In DNA repair, it upregulates GADD45 family members and repair genes such as DDB2 and XPC. In apoptosis, it activates pro-death genes including BAX, PUMA (BBC3), NOXA (PMAIP1), and APAF1. It also influences metabolism and redox balance through targets like TIGAR and the Sestrin family, contributing to cellular adaptation under stress.

Context dependence: The p53 regulon is large but highly context-specific, differing by cell type, tissue, and the nature of the stress. Not all p53-binding events cause expression changes, and many effects arise from indirect or combinatorial regulatory interactions with other transcription factors.

Clinical relevance: Dysregulation of p53 or its target genes is common in cancer. Therapeutic strategies often aim to restore p53 activity or to target downstream pathways controlled by p53-regulated genes.

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