NM0005465

NM_0005465 is a RefSeq mRNA entry in Homo sapiens that corresponds to a transcript of the TP53 gene, encoding the tumor protein p53.

The p53 protein is a transcription factor and tumor suppressor that coordinates cellular responses to stress, including DNA damage, oncogene activation, and hypoxia. It activates transcription of genes such as CDKN1A (p21), GADD45, BBC3 (PUMA), and PMAIP1 (NOXA), leading to cell cycle arrest, DNA repair, apoptosis, or senescence.

p53 activity is regulated by post-translational modifications and interactions; ATM/ATR-mediated phosphorylation, acetylation; MDM2/MDMX-mediated ubiquitination; stabilization in response to stress; forms a tetramer to bind DNA. The protein is about 393 amino acids in length and functions as a central node in a network that integrates signals from diverse cellular stresses.

Genomic and clinical significance: TP53 is the most frequently mutated gene in human cancers; germline TP53 mutations cause Li-Fraumeni syndrome, characterized by predisposition to a broad spectrum of early-onset cancers. Loss of p53 function leads to genomic instability and altered responses to DNA damage. Some cancers retain wild-type p53 but suppress its activity through overexpression of negative regulators like MDM2.

Genomic context and isoforms: TP53 is located on chromosome 17p13.1. The TP53 transcript family includes multiple mRNA splice variants and promoter-driven transcripts, yielding several p53 isoforms with distinct regulatory properties and functions.

Notes: NM_0005465 is an mRNA accession; researchers typically reference NM_000546 for the canonical TP53 transcript. If a different accession was intended, please verify the RefSeq entry.