Tumor protein p53-inducible nuclear protein 1 (TP53INP1)

TP53INP1 (tumor protein p53-inducible nuclear protein 1) is a stress-inducible nuclear protein critically upregulated by transcription factors like p53 and p73 in response to cellular stress or DNA damage. It regulates cell cycle arrest, apoptosis, and autophagy through multiple mechanisms including direct phosphorylation of p53, transcriptional regulation of genes such as p21 and Bax, and protein-protein interactions with autophagy mediators LC3 and GABARAP via a LC3-interacting region. TP53INP1 acts as a tumor suppressor, limiting cell proliferation and enhancing caspase-dependent and autophagy-dependent cell death, as well as contributing to cellular antioxidant responses. Loss or downregulation of TP53INP1 is implicated in early cancer progression and increased susceptibility to inflammation-induced carcinogenesis, particularly in pancreatic and colon tissues. It primarily localizes to the nucleus but relocalizes to autophagosomes during autophagy, where it is eventually degraded. Restoration or upregulation of TP53INP1 holds potential for anti-cancer therapies, especially in contexts where p53 is functional. No drugs currently target TP53INP1 directly, but its expression and function may be modulated via stress-inducing agents.

Other names

TP53INP1p53DINP1SIPTEAPTP53INP1ATP53INP1BStress-induced proteinDKFZp434M1317FLJ22139TP53DINP1Tumor protein p53-inducible nuclear protein 1p53-dependent damage-inducible nuclear protein 1

Transcriptional activation: Drugs that cause DNA damage or cellular stress (e.g., chemotherapeutics) can activate p53, leading to increased TP53INP1 expression; this in turn promotes cell cycle arrest, apoptosis, or autophagy. Positive feedback: By interacting with protein kinases (HIPK2, PKCδ), TP53INP1 phosphorylates and activates p53, enhancing transcription of pro-apoptotic and cell cycle arrest genes.