Group XVI phospholipase A2 also commonly known as adipocyte phospholipase A2 (AdPLA) is an enzyme that in humans is encoded by the PLA2G16gene.[1][2][3] This enzyme has also been identified as PLA2G16, HRASLS3, HREV107, HREV107-3, MGC118754 or H-REV107-1 from studies on class II tumor suppression but not on its enzymatic properties.[4] AdPLA is encoded by a 1.3 kilobase AdPLA messenger RNA and is an 18 kDa protein. It belongs to a superfamily of phospholipase A2 (PLA2) enzymes and is found primarily in adipose tissue. AdPLA regulates adipocyte lipolysis and release of fatty acids through a G-protein coupled pathway involving prostaglandin and EP3. It has also been reported to play a crucial role in the development of obesity in mouse models.[5]
Adipose Phospholipase A2
Crystallographic structure of Adipose Phospholipase A2 (AdPLA)
AdPLA has been characterized in Group XVI as a separate subgroup of the PLA2 family for its distinct properties from other known PLA2s. It bears similarity to its PLA2 family in phospholipase activity and calcium dependence. Unlike other PLA2 enzymes, AdPLA is expressed predominantly in adipose tissue at higher levels than in the rest of the body, more so in white adipose tissue (WAT) than brown adipose tissue (BAT). Its primary enzymatic function is to catalyze the preferential hydrolysis of phosphatidylcholines at the sn-2 position, generating free fatty acids.
AdPLA active site with labeled His-23 and Cys-113 residues are responsible for AdPLA catalysis.
AdPLA contains a membrane-spanning domain on the C-terminus, which localizes intracellularly for phospholipase activity in proximity to cyclooxygenase 1 (COX-1). His-23 and Cys-113 residues have been shown to be essential in AdPLA activity, which differs from the known His/Asp catalytic dyad or Ser/His/Asp catalytic triad of other PLA2 enzymes. Gln-129 and Asn-112 have also been shown to be necessary in catalysis but their role is not known.[2]
AdPLA activity is calcium and pH dependent. Calcium binds to AdPLA and forms a positively charged oxyanion hole to stabilize a negatively charged transition state, similar to other PLA2 active sites. Whereas asparagine binds to calcium in other PLA2 enzymes,[6] the residue that participates in the creation of oxyanion hole in AdPLA has not yet been verified. Optimum AdPLA activity occurs in relatively basic conditions, between pH 7 and 9, to facilitate formation of a histidine-water complex and subsequent fatty acid hydrolysis.[2]
Studies on AdPLA have shown lipolysis regulation following a G-protein coupled pathway in WAT.[5] WAT is responsible for releasing fatty acids from stored triacylglycerol as energy sources for other tissues which is regulated predominately by AdPLA over other phospholipase A2 enzymes. Lipolysis is inversely related to AdPLA activity. AdPLA catalyzes the rate-limiting step, production of arachidonic acid, for the production of prostaglandins, specifically prostaglandin E2 (PGE2). PGE2 enters the signaling pathway binding to G protein-coupled receptor (EP3) which inhibits adenylyl cyclase. Inhibition of adenylyl cyclase decreases the conversion of cyclic AMP (cAMP) from ATP. Lower levels of cAMP decrease the activity of protein kinase A to phosphorylate, thereby activating, hormone-sensitive lipase.[11] The opposite effect can be reached with inactivated AdPLA, decreasing PGE2 concentration and EP3 activity, leading to an increase in cAMP and lipase activity. This mechanism was postulated on the basis that the predominant signaling protein and receptor present in WAT are PGE2 and EP3. These results were based on a mouse model and although they are mammalian cells, it has not been shown to apply to human cells.
Effects on obesityedit
Obesity has been attributed to adipocyte hypertrophy, where triacylglycerol synthesis exceeds lipolysis, resulting in elevated triacylglycerol storage.[12] Previous studies have associated obesity with endocrine factors and have led pharmacological work toward hormone regulation.[13] Studies on AdPLA deficient mice have shown that the enzyme increased lipolysis in WAT as a result of decreased lipolysis regulation. AdPLA deficiency was shown to reduce adipose tissue mass for mice in both standard and high fat diets. Adipocyte hypotrophy was attributed primarily to reduced triacylglyceride content in WAT from lipolysis, while adipocyte differentiation did not play a role in reduced adipose tissue despite the effects of prostaglandins on adipogenesis.[14] AdPLA deficiency also led to higher oxygen consumption due to the upregulation of genes involved in oxidative metabolism, increasing fatty acid oxidation. One upregulated gene in particular, uncoupling protein-1 (UCP1), has been shown to reduce diet-induced obesity.[15]
Studies on AdPLA deficient and genetically obese mice (leptin deficiency) have also shown similar effects, reduced adipose tissue mass and increased lipolysis by reduction in PGE2 and EP3 activity. Fatty acid oxidation was also found to increase to levels of wild-type mice that were deficient in non-AdPLA deficient obese mice. Body composition also showed a higher percentage of water and lean tissue mass compared to non-AdPLA deficient obese mice.[5]
AdPLA deficiency also demonstrated adverse effects, increasing ectopic triglyceride storage and insulin resistance. Liver enlargement was attributed to higher fatty acid uptake and triacylglycerol content. Insulin stimulated glucose uptake and metabolism were also blunted in AdPLA deficiency, decreasing glycolysis and glycogen synthesis.[5] Despite these side effects, AdPLA is a novel breakthrough in studying autocrine and paracrine action of AdPLA in regulating obesity and fat metabolism. These side effects have triggered new studies to be performed on reduction of AdPLA function as opposed to complete ablation.[16]
Referencesedit
^Husmann K, Sers C, Fietze E, Mincheva A, Lichter P, Schäfer R (Oct 1998). "Transcriptional and translational downregulation of H-REV107, a class II tumour suppressor gene located on human chromosome 11q11-12". Oncogene. 17 (10): 1305–12. doi:10.1038/sj.onc.1202060. PMID 9771974.
^ abcDuncan RE, Sarkadi-Nagy E, Jaworski K, Ahmadian M, Sul HS (Sep 2008). "Identification and functional characterization of adipose-specific phospholipase A2 (AdPLA)". J Biol Chem. 283 (37): 25428–36. doi:10.1074/jbc.M804146200. PMC2533091. PMID 18614531.
^Sers C, Emmenegger U, Husmann K, Bucher K, Andres AC, Schäfer R (February 1997). "Growth-inhibitory activity and downregulation of the class II tumor-suppressor gene H-rev107 in tumor cell lines and experimental tumors". J. Cell Biol. 136 (4): 935–44. doi:10.1083/jcb.136.4.935. PMC2132501. PMID 9049257.
^ abcdJaworski K, Ahmadian M, Duncan RE, Sarkadi-Nagy E, Varady KA, Hellerstein MK, Lee HY, Samuel VT, Shulman GI, Kim KH, de Val S, Kang C, Sul HS (February 2009). "AdPLA ablation increases lipolysis and prevents obesity induced by high-fat feeding or leptin deficiency". Nat. Med. 15 (2): 159–68. doi:10.1038/nm.1904. PMC2863116. PMID 19136964.
^Six DA, Dennis EA (October 2000). "The expanding superfamily of phospholipase A(2) enzymes: classification and characterization". Biochim. Biophys. Acta. 1488 (1–2): 1–19. doi:10.1016/S1388-1981(00)00105-0. PMID 11080672. S2CID 23717374.
^ abcGRCh38: Ensembl release 89: ENSG00000176485 – Ensembl, May 2017
^ abcGRCm38: Ensembl release 89: ENSMUSG00000060675 – Ensembl, May 2017
^"Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^"Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^Richelsen B (November 1992). "Release and effects of prostaglandins in adipose tissue". Prostaglandins Leukot. Essent. Fatty Acids. 47 (3): 171–82. doi:10.1016/0952-3278(92)90235-B. PMID 1475271.
^Jaworski K, Sarkadi-Nagy E, Duncan RE, Ahmadian M, Sul HS (July 2007). "Regulation of triglyceride metabolism. IV. Hormonal regulation of lipolysis in adipose tissue". Am. J. Physiol. Gastrointest. Liver Physiol. 293 (1): G1–4. doi:10.1152/ajpgi.00554.2006. PMC2887286. PMID 17218471.
^Adan RA, Vanderschuren LJ, la Fleur SE (April 2008). "Anti-obesity drugs and neural circuits of feeding". Trends Pharmacol. Sci. 29 (4): 208–17. doi:10.1016/j.tips.2008.01.008. PMID 18353447.
^Fajas L, Miard S, Briggs MR, Auwerx J (September 2003). "Selective cyclo-oxygenase-2 inhibitors impair adipocyte differentiation through inhibition of the clonal expansion phase". J. Lipid Res. 44 (9): 1652–9. doi:10.1194/jlr.M300248-JLR200. PMID 12837847.
^Kopecký J, Hodný Z, Rossmeisl M, Syrový I, Kozak LP (May 1996). "Reduction of dietary obesity in aP2-Ucp transgenic mice: physiology and adipose tissue distribution". Am. J. Physiol. 270 (5 Pt 1): E768–75. doi:10.1152/ajpendo.1996.270.5.E768. PMID 8967464.
^News Staff. "Disabling AdPLA Enzyme Lets You Eat Anything And Never Get Obese, If..." ION Publications LLC. Retrieved 1 March 2012.
Further readingedit
Scanlan MJ, Gordan JD, Williamson B, Stockert E, Bander NH, Jongeneel V, Gure AO, Jäger D, Jäger E, Knuth A, Chen YT, Old LJ (1999). "Antigens recognized by autologous antibody in patients with renal-cell carcinoma". Int. J. Cancer. 83 (4): 456–64. doi:10.1002/(SICI)1097-0215(19991112)83:4<456::AID-IJC4>3.0.CO;2-5. PMID 10508479.
Siegrist S, Féral C, Chami M, Solhonne B, Mattéi MG, Rajpert-De Meyts E, Guellaën G, Bulle F (2001). "hH-Rev107, a class II tumor suppressor gene, is expressed by post-meiotic testicular germ cells and CIS cells but not by human testicular germ cell tumors". Oncogene. 20 (37): 5155–63. doi:10.1038/sj.onc.1204658. PMC1865474. PMID 11526504.
Sers C, Husmann K, Nazarenko I, Reich S, Wiechen K, Zhumabayeva B, Adhikari P, Schröder K, Gontarewicz A, Schäfer R (2002). "The class II tumour suppressor gene H-REV107-1 is a target of interferon-regulatory factor-1 and is involved in IFNgamma-induced cell death in human ovarian carcinoma cells". Oncogene. 21 (18): 2829–39. doi:10.1038/sj.onc.1205377. PMID 11973642.
Roder K, Kim KH, Sul HS (2002). "Induction of murine H-rev107 gene expression by growth arrest and histone acetylation: involvement of an Sp1/Sp3-binding GC-box". Biochem. Biophys. Res. Commun. 294 (1): 63–70. doi:10.1016/S0006-291X(02)00440-0. PMID 12054741.
Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, Berriz GF, Gibbons FD, Dreze M, Ayivi-Guedehoussou N, Klitgord N, Simon C, Boxem M, Milstein S, Rosenberg J, Goldberg DS, Zhang LV, Wong SL, Franklin G, Li S, Albala JS, Lim J, Fraughton C, Llamosas E, Cevik S, Bex C, Lamesch P, Sikorski RS, Vandenhaute J, Zoghbi HY, Smolyar A, Bosak S, Sequerra R, Doucette-Stamm L, Cusick ME, Hill DE, Roth FP, Vidal M (2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature. 437 (7062): 1173–8. Bibcode:2005Natur.437.1173R. doi:10.1038/nature04209. PMID 16189514. S2CID 4427026.
Lim J, Hao T, Shaw C, Patel AJ, Szabó G, Rual JF, Fisk CJ, Li N, Smolyar A, Hill DE, Barabási AL, Vidal M, Zoghbi HY (2006). "A protein-protein interaction network for human inherited ataxias and disorders of Purkinje cell degeneration". Cell. 125 (4): 801–14. doi:10.1016/j.cell.2006.03.032. PMID 16713569. S2CID 13709685.
Nazarenko I, Kristiansen G, Fonfara S, Guenther R, Gieseler C, Kemmner W, Schafer R, Petersen I, Sers C (2006). "H-REV107-1 stimulates growth in non-small cell lung carcinomas via the activation of mitogenic signaling". Am. J. Pathol. 169 (4): 1427–39. doi:10.2353/ajpath.2006.051341. PMC1698850. PMID 17003497.
Nazarenko I, Schäfer R, Sers C (2007). "Mechanisms of the HRSL3 tumor suppressor function in ovarian carcinoma cells". J. Cell Sci. 120 (Pt 8): 1393–404. doi:10.1242/jcs.000018. PMID 17374643.
hrasls3, group, phospholipase, also, commonly, known, adipocyte, phospholipase, adpla, enzyme, that, humans, encoded, pla2g16, gene, this, enzyme, also, been, identified, pla2g16, hrev107, hrev107, mgc118754, rev107, from, studies, class, tumor, suppression, e. Group XVI phospholipase A2 also commonly known as adipocyte phospholipase A2 AdPLA is an enzyme that in humans is encoded by the PLA2G16 gene 1 2 3 This enzyme has also been identified as PLA2G16 HRASLS3 HREV107 HREV107 3 MGC118754 or H REV107 1 from studies on class II tumor suppression but not on its enzymatic properties 4 AdPLA is encoded by a 1 3 kilobase AdPLA messenger RNA and is an 18 kDa protein It belongs to a superfamily of phospholipase A2 PLA2 enzymes and is found primarily in adipose tissue AdPLA regulates adipocyte lipolysis and release of fatty acids through a G protein coupled pathway involving prostaglandin and EP3 It has also been reported to play a crucial role in the development of obesity in mouse models 5 Adipose Phospholipase A2Crystallographic structure of Adipose Phospholipase A2 AdPLA IdentifiersEC no 3 1 1 4CAS no 9001 84 7DatabasesIntEnzIntEnz viewBRENDABRENDA entryExPASyNiceZyme viewKEGGKEGG entryMetaCycmetabolic pathwayPRIAMprofilePDB structuresRCSB PDB PDBe PDBsumGene OntologyAmiGO QuickGOSearchPMCarticlesPubMedarticlesNCBIproteins Contents 1 Enzyme characteristics 2 Function 3 Effects on obesity 4 References 5 Further readingEnzyme characteristics editAdPLA has been characterized in Group XVI as a separate subgroup of the PLA2 family for its distinct properties from other known PLA2s It bears similarity to its PLA2 family in phospholipase activity and calcium dependence Unlike other PLA2 enzymes AdPLA is expressed predominantly in adipose tissue at higher levels than in the rest of the body more so in white adipose tissue WAT than brown adipose tissue BAT Its primary enzymatic function is to catalyze the preferential hydrolysis of phosphatidylcholines at the sn 2 position generating free fatty acids nbsp AdPLA active site with labeled His 23 and Cys 113 residues are responsible for AdPLA catalysis AdPLA contains a membrane spanning domain on the C terminus which localizes intracellularly for phospholipase activity in proximity to cyclooxygenase 1 COX 1 His 23 and Cys 113 residues have been shown to be essential in AdPLA activity which differs from the known His Asp catalytic dyad or Ser His Asp catalytic triad of other PLA2 enzymes Gln 129 and Asn 112 have also been shown to be necessary in catalysis but their role is not known 2 AdPLA activity is calcium and pH dependent Calcium binds to AdPLA and forms a positively charged oxyanion hole to stabilize a negatively charged transition state similar to other PLA2 active sites Whereas asparagine binds to calcium in other PLA2 enzymes 6 the residue that participates in the creation of oxyanion hole in AdPLA has not yet been verified Optimum AdPLA activity occurs in relatively basic conditions between pH 7 and 9 to facilitate formation of a histidine water complex and subsequent fatty acid hydrolysis 2 Function editPLAAT3Available structuresPDBOrtholog search PDBe RCSBList of PDB id codes2KYT 4DOT 4FA0 4Q95IdentifiersAliasesPLAAT3 AdPLA H REV107 1 HRASLS3 HREV107 HREV107 1 HREV107 3 HRSL3 phospholipase A2 group XVI H REV107 PLAAT 3 PLA2G16 phospholipase A and acyltransferase 3External IDsOMIM 613867 MGI 2179715 HomoloGene 5136 GeneCards PLAAT3Gene location Human nbsp Chr Chromosome 11 human 7 nbsp nbsp nbsp Band11q12 3 q13 1Start63 573 195 bp 7 End63 616 883 bp 7 Gene location Mouse nbsp Chr Chromosome 19 mouse 8 nbsp nbsp nbsp Band19 19 AStart7 534 824 bp 8 End7 565 910 bp 8 RNA expression patternBgeeHumanMouse ortholog Top expressed incorpus callosumadipose tissueabdominal fattibial nerveinferior ganglion of vagus nervesubcutaneous adipose tissueexternal globus pallidusmiddle frontal gyrusputameninferior olivary nucleusTop expressed inwhite adipose tissuesubcutaneous adipose tissuesciatic nervebloodlensbrown adipose tissueintercostal musclesoleus musclemammary glandsternocleidomastoid muscleMore reference expression dataBioGPS nbsp More reference expression dataGene ontologyMolecular functionphosphatidylserine 1 acylhydrolase activity protein binding 1 acyl 2 lysophosphatidylserine acylhydrolase activity hydrolase activity phospholipase A2 activity acyltransferase activity phospholipase A1 activity N acyltransferase activityCellular componentcytoplasm integral component of membrane cytosol membrane endoplasmic reticulum perinuclear region of cytoplasm peroxisome peroxisomal membrane cellular componentBiological processphosphatidylserine acyl chain remodeling phosphatidylethanolamine acyl chain remodeling lipid metabolism negative regulation of cell cycle phosphatidylinositol acyl chain remodeling phospholipid biosynthetic process phosphatidylcholine acyl chain remodeling phospholipid metabolic process triglyceride metabolic process peroxisome organization lipid catabolic process ether lipid metabolic process regulation of adipose tissue development response to bacterium N acylphosphatidylethanolamine metabolic processSources Amigo QuickGOOrthologsSpeciesHumanMouseEntrez11145225845EnsemblENSG00000176485ENSMUSG00000060675UniProtP53816Q8R3U1RefSeq mRNA NM 001128203NM 007069NM 139269NM 001362425RefSeq protein NP 001121675NP 009000NP 644675NP 001349354Location UCSC Chr 11 63 57 63 62 MbChr 19 7 53 7 57 MbPubMed search 9 10 WikidataView Edit HumanView Edit MouseStudies on AdPLA have shown lipolysis regulation following a G protein coupled pathway in WAT 5 WAT is responsible for releasing fatty acids from stored triacylglycerol as energy sources for other tissues which is regulated predominately by AdPLA over other phospholipase A2 enzymes Lipolysis is inversely related to AdPLA activity AdPLA catalyzes the rate limiting step production of arachidonic acid for the production of prostaglandins specifically prostaglandin E2 PGE2 PGE2 enters the signaling pathway binding to G protein coupled receptor EP3 which inhibits adenylyl cyclase Inhibition of adenylyl cyclase decreases the conversion of cyclic AMP cAMP from ATP Lower levels of cAMP decrease the activity of protein kinase A to phosphorylate thereby activating hormone sensitive lipase 11 The opposite effect can be reached with inactivated AdPLA decreasing PGE2 concentration and EP3 activity leading to an increase in cAMP and lipase activity This mechanism was postulated on the basis that the predominant signaling protein and receptor present in WAT are PGE2 and EP3 These results were based on a mouse model and although they are mammalian cells it has not been shown to apply to human cells Effects on obesity editObesity has been attributed to adipocyte hypertrophy where triacylglycerol synthesis exceeds lipolysis resulting in elevated triacylglycerol storage 12 Previous studies have associated obesity with endocrine factors and have led pharmacological work toward hormone regulation 13 Studies on AdPLA deficient mice have shown that the enzyme increased lipolysis in WAT as a result of decreased lipolysis regulation AdPLA deficiency was shown to reduce adipose tissue mass for mice in both standard and high fat diets Adipocyte hypotrophy was attributed primarily to reduced triacylglyceride content in WAT from lipolysis while adipocyte differentiation did not play a role in reduced adipose tissue despite the effects of prostaglandins on adipogenesis 14 AdPLA deficiency also led to higher oxygen consumption due to the upregulation of genes involved in oxidative metabolism increasing fatty acid oxidation One upregulated gene in particular uncoupling protein 1 UCP1 has been shown to reduce diet induced obesity 15 Studies on AdPLA deficient and genetically obese mice leptin deficiency have also shown similar effects reduced adipose tissue mass and increased lipolysis by reduction in PGE2 and EP3 activity Fatty acid oxidation was also found to increase to levels of wild type mice that were deficient in non AdPLA deficient obese mice Body composition also showed a higher percentage of water and lean tissue mass compared to non AdPLA deficient obese mice 5 AdPLA deficiency also demonstrated adverse effects increasing ectopic triglyceride storage and insulin resistance Liver enlargement was attributed to higher fatty acid uptake and triacylglycerol content Insulin stimulated glucose uptake and metabolism were also blunted in AdPLA deficiency decreasing glycolysis and glycogen synthesis 5 Despite these side effects AdPLA is a novel breakthrough in studying autocrine and paracrine action of AdPLA in regulating obesity and fat metabolism These side effects have triggered new studies to be performed on reduction of AdPLA function as opposed to complete ablation 16 References edit Husmann K Sers C Fietze E Mincheva A Lichter P Schafer R Oct 1998 Transcriptional and translational downregulation of H REV107 a class II tumour suppressor gene located on human chromosome 11q11 12 Oncogene 17 10 1305 12 doi 10 1038 sj onc 1202060 PMID 9771974 a b c Duncan RE Sarkadi Nagy E Jaworski K Ahmadian M Sul HS Sep 2008 Identification and functional characterization of adipose specific phospholipase A2 AdPLA J Biol Chem 283 37 25428 36 doi 10 1074 jbc M804146200 PMC 2533091 PMID 18614531 Entrez Gene HRASLS3 HRAS like suppressor 3 Sers C Emmenegger U Husmann K Bucher K Andres AC Schafer R February 1997 Growth inhibitory activity and downregulation of the class II tumor suppressor gene H rev107 in tumor cell lines and experimental tumors J Cell Biol 136 4 935 44 doi 10 1083 jcb 136 4 935 PMC 2132501 PMID 9049257 a b c d Jaworski K Ahmadian M Duncan RE Sarkadi Nagy E Varady KA Hellerstein MK Lee HY Samuel VT Shulman GI Kim KH de Val S Kang C Sul HS February 2009 AdPLA ablation increases lipolysis and prevents obesity induced by high fat feeding or leptin deficiency Nat Med 15 2 159 68 doi 10 1038 nm 1904 PMC 2863116 PMID 19136964 Six DA Dennis EA October 2000 The expanding superfamily of phospholipase A 2 enzymes classification and characterization Biochim Biophys Acta 1488 1 2 1 19 doi 10 1016 S1388 1981 00 00105 0 PMID 11080672 S2CID 23717374 a b c GRCh38 Ensembl release 89 ENSG00000176485 Ensembl May 2017 a b c GRCm38 Ensembl release 89 ENSMUSG00000060675 Ensembl May 2017 Human PubMed Reference National Center for Biotechnology Information U S National Library of Medicine Mouse PubMed Reference National Center for Biotechnology Information U S National Library of Medicine Richelsen B November 1992 Release and effects of prostaglandins in adipose tissue Prostaglandins Leukot Essent Fatty Acids 47 3 171 82 doi 10 1016 0952 3278 92 90235 B PMID 1475271 Jaworski K Sarkadi Nagy E Duncan RE Ahmadian M Sul HS July 2007 Regulation of triglyceride metabolism IV Hormonal regulation of lipolysis in adipose tissue Am J Physiol Gastrointest Liver Physiol 293 1 G1 4 doi 10 1152 ajpgi 00554 2006 PMC 2887286 PMID 17218471 Adan RA Vanderschuren LJ la Fleur SE April 2008 Anti obesity drugs and neural circuits of feeding Trends Pharmacol Sci 29 4 208 17 doi 10 1016 j tips 2008 01 008 PMID 18353447 Fajas L Miard S Briggs MR Auwerx J September 2003 Selective cyclo oxygenase 2 inhibitors impair adipocyte differentiation through inhibition of the clonal expansion phase J Lipid Res 44 9 1652 9 doi 10 1194 jlr M300248 JLR200 PMID 12837847 Kopecky J Hodny Z Rossmeisl M Syrovy I Kozak LP May 1996 Reduction of dietary obesity in aP2 Ucp transgenic mice physiology and adipose tissue distribution Am J Physiol 270 5 Pt 1 E768 75 doi 10 1152 ajpendo 1996 270 5 E768 PMID 8967464 News Staff Disabling AdPLA Enzyme Lets You Eat Anything And Never Get Obese If ION Publications LLC Retrieved 1 March 2012 Further reading editScanlan MJ Gordan JD Williamson B Stockert E Bander NH Jongeneel V Gure AO Jager D Jager E Knuth A Chen YT Old LJ 1999 Antigens recognized by autologous antibody in patients with renal cell carcinoma Int J Cancer 83 4 456 64 doi 10 1002 SICI 1097 0215 19991112 83 4 lt 456 AID IJC4 gt 3 0 CO 2 5 PMID 10508479 Siegrist S Feral C Chami M Solhonne B Mattei MG Rajpert De Meyts E Guellaen G Bulle F 2001 hH Rev107 a class II tumor suppressor gene is expressed by post meiotic testicular germ cells and CIS cells but not by human testicular germ cell tumors Oncogene 20 37 5155 63 doi 10 1038 sj onc 1204658 PMC 1865474 PMID 11526504 Sers C Husmann K Nazarenko I Reich S Wiechen K Zhumabayeva B Adhikari P Schroder K Gontarewicz A Schafer R 2002 The class II tumour suppressor gene H REV107 1 is a target of interferon regulatory factor 1 and is involved in IFNgamma induced cell death in human ovarian carcinoma cells Oncogene 21 18 2829 39 doi 10 1038 sj onc 1205377 PMID 11973642 Roder K Kim KH Sul HS 2002 Induction of murine H rev107 gene expression by growth arrest and histone acetylation involvement of an Sp1 Sp3 binding GC box Biochem Biophys Res Commun 294 1 63 70 doi 10 1016 S0006 291X 02 00440 0 PMID 12054741 Rual JF Venkatesan K Hao T Hirozane Kishikawa T Dricot A Li N Berriz GF Gibbons FD Dreze M Ayivi Guedehoussou N Klitgord N Simon C Boxem M Milstein S Rosenberg J Goldberg DS Zhang LV Wong SL Franklin G Li S Albala JS Lim J Fraughton C Llamosas E Cevik S Bex C Lamesch P Sikorski RS Vandenhaute J Zoghbi HY Smolyar A Bosak S Sequerra R Doucette Stamm L Cusick ME Hill DE Roth FP Vidal M 2005 Towards a proteome scale map of the human protein protein interaction network Nature 437 7062 1173 8 Bibcode 2005Natur 437 1173R doi 10 1038 nature04209 PMID 16189514 S2CID 4427026 Lim J Hao T Shaw C Patel AJ Szabo G Rual JF Fisk CJ Li N Smolyar A Hill DE Barabasi AL Vidal M Zoghbi HY 2006 A protein protein interaction network for human inherited ataxias and disorders of Purkinje cell degeneration Cell 125 4 801 14 doi 10 1016 j cell 2006 03 032 PMID 16713569 S2CID 13709685 Nazarenko I Kristiansen G Fonfara S Guenther R Gieseler C Kemmner W Schafer R Petersen I Sers C 2006 H REV107 1 stimulates growth in non small cell lung carcinomas via the activation of mitogenic signaling Am J Pathol 169 4 1427 39 doi 10 2353 ajpath 2006 051341 PMC 1698850 PMID 17003497 Nazarenko I Schafer R Sers C 2007 Mechanisms of the HRSL3 tumor suppressor function in ovarian carcinoma cells J Cell Sci 120 Pt 8 1393 404 doi 10 1242 jcs 000018 PMID 17374643 Portal nbsp Biology Retrieved from https en wikipedia org w index php title HRASLS3 amp oldid 1172349911, wikipedia, wiki, book, books, library,
