{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nRecent studies have shown that PLAAT3—also known by names such as PLA2G16, H‐REV107, AdPLA, and PLA/AT‐3—plays a central role in lipid and energy metabolism. In adipocytes, PLAAT3 regulates lipolysis and triglyceride storage as well as energy expenditure. For example, characterization of adipose‐specific PLA2 activity demonstrated that PLAAT3 hydrolyzes phospholipids to release free fatty acids and lysophospholipids, thereby modulating cAMP levels and prostaglandin signaling to control lipolysis and adiposity. Moreover, structural and biochemical evaluations have revealed a unique catalytic mechanism (involving a distinctive Cys–His–His triad) and dual PLA₁/PLA₂ activity that underpins its regulatory effects on fat metabolism, including in liver cells and conditions such as peripheral artery disease."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "6"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to metabolic regulation, PLAAT3 is emerging as a key modulator of tumor behavior. In several cancer types—including osteosarcoma, pancreatic adenocarcinoma, colorectal cancer, lung carcinoma, and prostate cancer—elevated PLAAT3 expression (often driven by mutant p53 or epigenetic alterations) has been linked to increased cell migration, invasion, and metastatic potential. Mechanistic studies have implicated PLAAT3 in regulating RAS activity and MAPK signaling, in part by modulating H‐RAS levels and interacting with factors such as ETS2 and TIG3 to affect tumor cell proliferation and apoptosis. Moreover, polymorphisms and methylation changes in the PLAAT3 gene locus have been associated with enhanced cancer risk and poorer patient prognosis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "7", "end_ref": "18"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its roles in metabolism and oncogenesis, PLAAT3 has been implicated in additional cellular processes. Notably, it has been identified as a host factor required early in the infectious cycle of picornaviruses, where its lipid‐modifying activity facilitates viral genome delivery into the cytoplasm while counteracting autophagic clearance mechanisms. Moreover, PLAAT3 can interact with peroxin Pex19p to interfere with the assembly of peroxisomal membrane proteins, thereby regulating peroxisome biogenesis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "19"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Robin E Duncan, Eszter Sarkadi-Nagy, Kathy Jaworski, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Identification and functional characterization of adipose-specific phospholipase A2 (AdPLA)."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M804146200"}], "href": "https://doi.org/10.1074/jbc.M804146200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18614531"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18614531"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Kathy Jaworski, Maryam Ahmadian, Robin E Duncan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "AdPLA ablation increases lipolysis and prevents obesity induced by high-fat feeding or leptin deficiency."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Med (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nm.1904"}], "href": "https://doi.org/10.1038/nm.1904"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19136964"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19136964"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Marcin Golczak, Philip D Kiser, Avery E Sears, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Structural basis for the acyltransferase activity of lecithin:retinol acyltransferase-like proteins."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M112.361550"}], "href": "https://doi.org/10.1074/jbc.M112.361550"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22605381"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22605381"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Xiao-Yan Pang, Jian Cao, Linsee Addington, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Structure/function relationships of adipose phospholipase A2 containing a cys-his-his catalytic triad."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M112.398859"}], "href": "https://doi.org/10.1074/jbc.M112.398859"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22923616"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22923616"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Fu-Ming Tsai, Mao-Liang Chen, Lu-Kai Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "H-rev107 Regulates Cytochrome P450 Reductase Activity and Increases Lipid Accumulation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0138586"}], "href": "https://doi.org/10.1371/journal.pone.0138586"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26381418"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26381418"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Caitlin Parmer, Ana Luisa De Sousa-Coelho, Henry S Cheng, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Skeletal muscle expression of adipose-specific phospholipase in peripheral artery disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Vasc Med (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1177/1358863X20947467"}], "href": "https://doi.org/10.1177/1358863X20947467"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32853041"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32853041"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Karim Roder, Kee-Hong Kim, Hei Sook Sul "}, {"type": "b", "children": [{"type": "t", "text": "Induction of murine H-rev107 gene expression by growth arrest and histone acetylation: involvement of an Sp1/Sp3-binding GC-box."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/S0006-291X(02)00440-0"}], "href": "https://doi.org/10.1016/S0006-291X(02"}, {"type": "t", "text": "00440-0) PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12054741"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12054741"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Irina Nazarenko, Glen Kristiansen, Sabine Fonfara, et al. "}, {"type": "b", "children": [{"type": "t", "text": "H-REV107-1 stimulates growth in non-small cell lung carcinomas via the activation of mitogenic signaling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Pathol (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.2353/ajpath.2006.051341"}], "href": "https://doi.org/10.2353/ajpath.2006.051341"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17003497"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17003497"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Irina Nazarenko, Marcel Jenny, Jana Keil, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Atypical protein kinase C zeta exhibits a proapoptotic function in ovarian cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cancer Res (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/1541-7786.MCR-09-0358"}], "href": "https://doi.org/10.1158/1541-7786.MCR-09-0358"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20501645"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20501645"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Chun-Hua Wang, Rong-Yaun Shyu, Chang-Chieh Wu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Phospholipase A/Acyltransferase enzyme activity of H-rev107 inhibits the H-RAS signaling pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biomed Sci (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/1423-0127-21-36"}], "href": "https://doi.org/10.1186/1423-0127-21-36"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24884338"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24884338"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Shunbin Xiong, Huolin Tu, Madhusudhan Kollareddy, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Pla2g16 phospholipase mediates gain-of-function activities of mutant p53."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.1404139111"}], "href": "https://doi.org/10.1073/pnas.1404139111"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25024203"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25024203"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Marcin Golczak, Avery E Sears, Philip D Kiser, et al. "}, {"type": "b", "children": [{"type": "t", "text": "LRAT-specific domain facilitates vitamin A metabolism by domain swapping in HRASLS3."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Chem Biol (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nchembio.1687"}], "href": "https://doi.org/10.1038/nchembio.1687"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25383759"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25383759"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Hejia Wei, Lei Wang, Xiaobai Ren, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Structural and functional characterization of tumor suppressors TIG3 and H-REV107."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "FEBS Lett (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.febslet.2015.04.002"}], "href": "https://doi.org/10.1016/j.febslet.2015.04.002"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25871522"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25871522"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "Shoulei Liang, Zhiwu Ren, Xiuxin Han, et al. "}, {"type": "b", "children": [{"type": "t", "text": "PLA2G16 Expression in Human Osteosarcoma Is Associated with Pulmonary Metastasis and Poor Prognosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0127236"}], "href": "https://doi.org/10.1371/journal.pone.0127236"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25993412"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25993412"}]}, {"type": "r", "ref": 15, "children": [{"type": "t", "text": "Lin Li, Shoulei Liang, Amanda R Wasylishen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "PLA2G16 promotes osteosarcoma metastasis and drug resistance via the MAPK pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncotarget (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.18632/oncotarget.7694"}], "href": "https://doi.org/10.18632/oncotarget.7694"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26933804"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26933804"}]}, {"type": "r", "ref": 16, "children": [{"type": "t", "text": "Xiao-Nv Xie, Jing Yu, Li-Hua Zhang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Relationship between polymorphisms of the lipid metabolism-related gene PLA2G16 and risk of colorectal cancer in the Chinese population."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Funct Integr Genomics (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s10142-018-0642-8"}], "href": "https://doi.org/10.1007/s10142-018-0642-8"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30343388"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30343388"}]}, {"type": "r", "ref": 17, "children": [{"type": "t", "text": "William E Jarrard, Adam Schultz, Tyler Etheridge, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Screening of urine identifies PLA2G16 as a field defect methylation biomarker for prostate cancer detection."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0218950"}], "href": "https://doi.org/10.1371/journal.pone.0218950"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31233548"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31233548"}]}, {"type": "r", "ref": 18, "children": [{"type": "t", "text": "Wei Xia, Hansong Bai, Ying Deng, et al. "}, {"type": "b", "children": [{"type": "t", "text": "PLA2G16 is a mutant p53/KLF5 transcriptional target and promotes glycolysis of pancreatic cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Mol Med (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/jcmm.15832"}], "href": "https://doi.org/10.1111/jcmm.15832"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32985124"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32985124"}]}, {"type": "r", "ref": 19, "children": [{"type": "t", "text": "Jacqueline Staring, Eleonore von Castelmur, Vincent A Blomen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "PLA2G16 represents a switch between entry and clearance of Picornaviridae."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nature (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nature21032"}], "href": "https://doi.org/10.1038/nature21032"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28077878"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28077878"}]}, {"type": "r", "ref": 20, "children": [{"type": "t", "text": "Toru Uyama, Katsuhisa Kawai, Nozomu Kono, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Interaction of Phospholipase A/Acyltransferase-3 with Pex19p: A POSSIBLE INVOLVEMENT IN THE DOWN-REGULATION OF PEROXISOMES."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M114.635433"}], "href": "https://doi.org/10.1074/jbc.M114.635433"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26018079"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26018079"}]}]}]}