Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P04637 (p53)
 77,613 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Apoptosis-inducing factor (AIF) is a mitochondrial flavoprotein that triggers caspase-independent apoptosis. We describe here the cloning and characterization of a novel AIF-homologous molecule designated AMID (AIF-homologous mitochondrion-associated inducer of death). AMID lacks a mitochondrial localization sequence but shares significant homology with AIF and NADH oxidoreductases from bacteria to mammalian species. Immunofluorescent staining and biochemical experiments indicated that AMID was co-localized with mitochondria. Overexpression of AMID induced cell death with characteristic apoptotic morphology. Furthermore, AMID-induced apoptosis was independent of caspase activation and p53 and was not inhibited by Bcl-2. These findings suggest that AMID induces a novel caspase-independent apoptotic pathway.
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PMID:AMID, an apoptosis-inducing factor-homologous mitochondrion-associated protein, induces caspase-independent apoptosis. 1198 Sep 7

The p53 tumor suppressor protein induces cell cycle arrest or apoptosis in response to cellular stresses. We have identified PRG3 (p53-responsive gene 3), which is induced specifically under p53-dependent apoptotic conditions in human colon cancer cells, and encodes a novel polypeptide of 373 amino acids with a predicted molecular mass of 40.5 kDa. PRG3 has significant homology to bacterial oxidoreductases and the apoptosis-inducing factor, AIF, and the gene was assigned to chromosome 10q21.3-q22.1. Expression of PRG3 was induced by the activation of endogenous p53 and it contains a p53-responsive element. Unlike AIF, PRG3 localizes in the cytoplasm and its ectopic expression induces apoptosis. An amino-terminal deletion mutant of PRG3 that lacks a putative oxidoreductase activity retains its apoptotic activity, suggesting that the oxidoreductase activity is dispensable for the apoptotic function of PRG3. The PRG3 gene is thus a novel p53 target gene in a p53-dependent apoptosis pathway.
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PMID:A novel p53-inducible apoptogenic gene, PRG3, encodes a homologue of the apoptosis-inducing factor (AIF). 1213 61

AMID, also called PRG3, is an AIF-homologous and mitochondria-associated protein that has been implicated in caspase-independent apoptosis. In this report, we demonstrated that human AMID gene promoter was activated by p53 in reporter gene assays. Chromatin immunoprecipitation experiments indicated that p53 could bind to human AMID promoter. Deletion mutagenesis indicated that human AMID promoter contains two p53-responsive elements. Furthermore, expression array analysis indicated that human AMID mRNA expression was downregulated in a majority of human tumors. Our findings point to the possibility that AMID is a p53-downstream gene involved in tumorigenesis.
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PMID:AMID is a p53-inducible gene downregulated in tumors. 1527 40

AMID is an apoptosis-inducing factor (AIF)-homologous and mitochondria-associated protein that has been implicated in caspase-independent apoptosis. Transcription of human AMID gene is upregulated by p53 and downregulated in tumors in comparison to their matched normal tissues, suggesting the possibility that AMID is involved in the downstream effects of p53. To investigate the physiological functions of AMID, we generated AMID-deficient mice by gene targeting. AMID-deficient mice are viable and fertile, develop normally and lack obvious phenotypic changes compared to wild-type mice up to 1 year old. AMID(-/-) mice up to 1 year old have no spontaneous tumors and show similar fibrosarcoma incidence after MCA inoculation compared to wild-type mice. AMID(-/-) embryonic fibroblasts exhibit normal proliferation but slightly increased resistance to genotoxin-induced growth arrest. These findings suggest that AMID is not required for normal development and p53-mediated tumor suppression.
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PMID:The p53-inducible apoptotic protein AMID is not required for normal development and tumor suppression. 1618 96

Background: There is no curative therapy for severe acute pancreatitis (SAP) due to poor understanding of its molecular mechanisms. Endoplasmic reticulum (ER) stress is involved in SAP and increased expression of ATF6 has been detected in SAP patients. Here, we aimed to investigate the role of ATF6 in a preclinical SAP mouse model and characterize its regulatory mechanism. Methods: Pancreatic tissues of healthy and SAP patients were collected during surgery. Humanized PRSS1 transgenic mice were treated with caerulein to mimic the SAP development, which was crossed to an ATF6 knockout mouse line, and pancreatic tissues from the resulting pups were screened by proteomics. Adenovirus-mediated delivery to the pancreas of SAP mice was used for shRNA-based knockdown or overexpression. The potential functions and mechanisms of ATF6 were clarified by immunofluorescence, immunoelectron microscopy, Western blotting, qRT-PCR, ChIP-qPCR and luciferase reporter assay. Results: Increased expression of ATF6 was associated with elevated apoptosis, ER and mitochondrial disorder in pancreatic tissues from SAP patients and PRSS1 mice. Knockout of ATF6 in SAP mice attenuated acinar injury, apoptosis and ER disorder. AIFM2, known as a p53 target gene, was identified as a downstream regulatory partner of ATF6, whose expression was increased in SAP. Functionally, AIFM2 could reestablish the pathological disorder in SAP tissues in the absence of ATF6. p53 expression was also increased in SAP mice, which was downregulated by ATF6 knockout. p53 knockout significantly suppressed acinar apoptosis and injury in SAP model. Mechanistically, ATF6 promoted AIFM2 transcription by binding to p53 and AIFM2 promoters. Conclusion: These results reveal that ATF6/p53/AIFM2 pathway plays a critical role in acinar apoptosis during SAP progression, highlighting novel therapeutic target molecules for SAP.
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PMID:ATF6 aggravates acinar cell apoptosis and injury by regulating p53/AIFM2 transcription in Severe Acute Pancreatitis. 3272 72

Ferroptosis was first coined in 2012 to describe the form of regulated cell death (RCD) characterized by iron-dependent lipid peroxidation. To date, ferroptosis has been implicated in many diseases, such as carcinogenesis, degenerative diseases (e.g., Huntington's, Alzheimer's, and Parkinson's diseases), ischemia-reperfusion injury, and cardiovascular diseases. Previous studies have identified numerous targets involved in ferroptosis; for example, acyl-CoA synthetase long-chain family member 4 (ACSL4) and p53 induce while glutathione peroxidase 4 (GPX4) and apoptosis-inducing factor mitochondria-associated 2 (AIFM2, also known as FSP1) inhibit ferroptosis. At least three major pathways (the glutathione-GPX4, FSP1-coenzyme Q10 (CoQ10), and GTP cyclohydrolase-1- (GCH1-) tetrahydrobiopterin (BH4) pathways) have been identified to participate in ferroptosis regulation. Recent advances have also highlighted the crucial roles of posttranslational modifications (PTMs) of proteins in ferroptosis. Here, we summarize the recently discovered knowledge regarding the mechanisms underlying ferroptosis, particularly the roles of PTMs in ferroptosis regulation.
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PMID:Posttranslational Modifications in Ferroptosis. 3329 26