Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P42574 (caspase-3)
 45,978 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Apoptosis is a genetically determined cell suicidal program that plays critical roles in many physiological and pathological processes. In this study, we report the cloning and characterization of a novel human gene, nuclear apoptosis-inducing factor 1 (NAIF1), overexpression of which induces apoptosis in cells. Human NAIF1 is located on chromosome 9q34.11 and encodes 327 amino acids with a homeodomain-like region and two nuclear localization signals at its N-terminal region. NAIF1 is conserved across diverse species, including human, mouse, crab-eating macaque, dog, chicken and frog, and shares no obvious homology to any known genes or proteins. Northern blot analysis revealed wide expression of NAIF1 mRNA throughout human tissues. NAIF1 was predominantly localized in the nucleus. Overexpression of NAIF1 inhibited cell growth and induced apoptosis. Furthermore, NAIF1 transfection caused both decreases in mitochondrial membrane potential and caspase-3 activation. In summary, NAIF1 is a nuclear protein that induces apoptosis when overexpressed.
 ...
PMID:Overexpression of the novel human gene, nuclear apoptosis-inducing factor 1, induces apoptosis. 1637 48

Many key proteins are down-regulated or lose their function during cancer genesis and accelerate the progress of cancer. We found that nuclear apoptosis-inducing factor 1 (NAIF1) was highly expressed in normal gastric tissues but was down-regulated or lost in gastric cancer tissues (P<0.001). NAIF1 expression was higher in well-differentiated (P=0.004) than in moderately- or poorly-differentiated gastric cancer. NAIF1 expression was associated with different T stages (P=0.024). In vitro, NAIF1 can inhibit tumor cell proliferation and induce G0/G1 phase cell cycle arrest in the MKN45 cell line. NAIF1 can induce apoptosis through activation of procaspase-9 rather than procaspase-8 followed by activation of the caspase-3 pathway. We designed and constructed two truncation mutants, pEGFP-N1-NLS and pEGFP-N1-GRR, and identified the N-terminal 1-90 amino acid domain of NAIF1, which is a helix-turn-helix motif and which was sufficient for inducing apoptosis. Therefore, these findings suggest that NAIF1 plays an inhibitory role in the initial steps of gastric cancer genesis and may provide new strategies for developing anti-cancer drugs using small molecular polypeptides.
 ...
PMID:NAIF1 is down-regulated in gastric cancer and promotes apoptosis through the caspase-9 pathway in human MKN45 cells. 2128 69