ArticleThe Journal of biological chemistry2013
Human and viral Golgi anti-apoptotic proteins (GAAPs) oligomerize via different mechanisms and monomeric GAAP inhibits apoptosis and modulates calcium.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 37 citations in OpenAlex.
- Article
- Article
- Regulation of mitochondrial proteostasis by the proton gradient.The EMBO journal · 2022Article
- Control of lysosomal-mediated cell death by the pH-dependent calcium channel RECS1.Science advances · 2021Article
- Poxviral Strategies to Overcome Host Cell Apoptosis.Pathogens (Basel, Switzerland) · 2020Review
- Golgi Structure and Function in Health, Stress, and Diseases.Results and problems in cell differentiation · 2019Review
- Article
- Vaccinia Virus Encodes a Novel Inhibitor of Apoptosis That Associates with the Apoptosome.Journal of virology · 2017Article
- Review
- TMBIM-mediated CaBiochimica et biophysica acta. Molecular cell research · 2017Review
- Review
- Review
- Golgi anti-apoptotic proteins are highly conserved ion channels that affect apoptosis and cell migration.The Journal of biological chemistry · 2015Article
- TaHsfA6f is a transcriptional activator that regulates a suite of heat stress protection genes in wheat (Triticum aestivum L.) including previously unknown Hsf targets.Journal of experimental botany · 2015Article
- TMBIM protein family: ancestral regulators of cell death.Oncogene · 2015Review
- Analysis of the anti-apoptotic activity of four vaccinia virus proteins demonstrates that B13 is the most potent inhibitor in isolation and during viral infection.The Journal of general virology · 2014Article
- Rolling-circle transposons catalyze genomic innovation in a mammalian lineage.Genome biology and evolution · 2014Article
- Pseudogenization of testis-specific Lfg5 predates human/Neanderthal divergence.Journal of human genetics · 2014Article
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
Golgi anti-apoptotic proteins (GAAPs) are hydrophobic proteins resident in membranes of the Golgi complex. They protect cells from a range of apoptotic stimuli, reduce the Ca(2+) content of intracellular stores, and regulate Ca(2+) fluxes. GAAP was discovered in camelpox virus, but it is highly conserved throughout evolution and encoded by all eukaryote genomes examined. GAAPs are part of the transmembrane Bax inhibitor-containing motif (TMBIM) family that also includes other anti-apoptotic and Ca(2+)-modulating membrane proteins. Most TMBIM members show multiple bands when analyzed by SDS-PAGE, suggesting that they may be oligomeric. However, the molecular mechanisms of oligomerization, the native state of GAAPs in living cells and the functional significance of oligomerization have not been addressed. TMBIM members are thought to have evolved from an ancestral GAAP. Two different GAAPs, human (h) and viral (v)GAAP were therefore selected as models to examine oligomerization of TMBIM family members. We show that both hGAAP and vGAAP in their native states form oligomers and that oligomerization is pH-dependent. Surprisingly, hGAAP and vGAAP do not share the same oligomerization mechanism. Oligomerization of hGAAP is independent of cysteines, but oligomerization of vGAAP depends on cysteines 9 and 60. A mutant vGAAP that is unable to oligomerize revealed that monomeric vGAAP retains both its anti-apoptotic function and its effect on intracellular Ca(2+) stores. In conclusion, GAAP can oligomerize in a pH-regulated manner, and monomeric GAAP is functional.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.