{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T22:08:53Z","timestamp":1787004533357,"version":"build-2736575974"},"reference-count":76,"publisher":"Portland Press Ltd.","issue":"21","content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2019,11,15]]},"abstract":"<jats:p>Aromatase CYP19A1 catalyzes the synthesis of estrogens in endocrine, reproductive and central nervous systems. Higher levels of 17\u03b2-estradiol (E2) are associated with malignancies and diseases of the breast, ovary and endometrium, while low E2 levels increase the risk for osteoporosis, cardiovascular diseases and cognitive disorders. E2, the transcriptional activator of the estrogen receptors, is also known to be involved in non-genomic signaling as a neurotransmitter\/neuromodulator, with recent evidence for rapid estrogen synthesis (RES) within the synaptic terminal. Although regulation of brain aromatase activity by phosphorylation\/dephosphorylation has been suggested, it remains obscure in the endocrine and reproductive systems. RES and overabundance of estrogens could stimulate the genomic and non-genomic signaling pathways, and genotoxic effects of estrogen metabolites. Here, by utilizing biochemical, cellular, mass spectrometric, and structural data we unequivocally demonstrate phosphorylation of human placental aromatase and regulation of its activity. We report that human aromatase has multiple phosphorylation sites, some of which are consistently detectable. Phosphorylation of the residue Y361 at the reductase-coupling interface significantly elevates aromatase activity. Other sites include the active site residue S478 and several at the membrane interface. We present the evidence that two histidine residues are phosphorylated. Furthermore, oxidation of two proline residues near the active site may have implications in regulation. Taken together, the results demonstrate that aromatase activity is regulated by phosphorylation and possibly other post-translational modifications. Protein level regulation of aromatase activity not only represents a paradigm shift in estrogen-mediated biology, it could also explain unresolved clinical questions such as aromatase inhibitor resistance.<\/jats:p>","DOI":"10.1042\/bcj20190633","type":"journal-article","created":{"date-parts":[[2019,10,14]],"date-time":"2019-10-14T11:17:56Z","timestamp":1571051876000},"page":"3313-3331","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Phosphorylation of human placental aromatase\n                    <i>CYP19A1<\/i>"],"prefix":"10.1042","volume":"476","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8810-6392","authenticated-orcid":false,"given":"Debashis","family":"Ghosh","sequence":"first","affiliation":[{"name":"Department of Pharmacology, State University of New York Upstate Medical University, Syracuse, NY 13210, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chinaza","family":"Egbuta","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, State University of New York Upstate Medical University, Syracuse, NY 13210, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean E.","family":"Kanyo","sequence":"additional","affiliation":[{"name":"Keck MS & Proteomics Resource, WM Keck Biotechnology Resource Laboratory, New Haven, CT 06510, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"TuKiet T.","family":"Lam","sequence":"additional","affiliation":[{"name":"Keck MS & Proteomics Resource, WM Keck Biotechnology Resource Laboratory, New Haven, CT 06510, U.S.A."},{"name":"Department of Molecular Biophysics and Biochemistry, Yale University School of Medicine, New Haven, CT 06520, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2019,11,11]]},"reference":[{"key":"2021112218022815000_BCJ-2019-0633C1","doi-asserted-by":"publisher","first-page":"343","DOI":"10.1210\/er.2008-0016","article-title":"History of aromatase: saga of an important biological mediator and therapeutic target","volume":"30","year":"2009","journal-title":"Endocr. Rev."},{"key":"2021112218022815000_BCJ-2019-0633C2","doi-asserted-by":"publisher","first-page":"8948","DOI":"10.1073\/pnas.85.23.8948","article-title":"Isolation of a full-length cDNA insert encoding human aromatase system cytochrome P-450 and its expression in nonsteroidogenic cells","volume":"85","year":"1988","journal-title":"Proc. Natl Acad. Sci. U.S.A."},{"key":"2021112218022815000_BCJ-2019-0633C3","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1146\/annurev.physiol.64.081601.142703","article-title":"Aromatase-a brief overview","volume":"64","year":"2002","journal-title":"Annu. Rev. Physiol."},{"key":"2021112218022815000_BCJ-2019-0633C4","unstructured":"American Cancer Society. (2017) Hormone therapy for breast cancer. https:\/\/www.cancer.org\/cancer\/breast-cancer\/treatment\/hormone-therapy-for-breast-cancer.html"},{"key":"2021112218022815000_BCJ-2019-0633C5","doi-asserted-by":"publisher","first-page":"270","DOI":"10.1056\/NEJMra050776","article-title":"Estrogen carcinogenesis in breast cancer","volume":"354","year":"2006","journal-title":"N. Engl. J. Med."},{"key":"2021112218022815000_BCJ-2019-0633C6","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1210\/edrv.21.1.0386","article-title":"Is estradiol a genotoxic mutagenic carcinogen?","volume":"21","year":"2000","journal-title":"Endocr. Rev."},{"key":"2021112218022815000_BCJ-2019-0633C7","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1016\/j.steroids.2014.08.003","article-title":"Estrogen metabolites and breast cancer","volume":"99","year":"2015","journal-title":"Steroids"},{"key":"2021112218022815000_BCJ-2019-0633C8","doi-asserted-by":"publisher","first-page":"918","DOI":"10.1158\/0008-5472.CAN-16-1717","article-title":"Association of estrogen metabolism with breast cancer risk in different cohorts of postmenopausal women","volume":"77","year":"2017","journal-title":"Cancer Res."},{"key":"2021112218022815000_BCJ-2019-0633C9","doi-asserted-by":"publisher","first-page":"696","DOI":"10.1158\/0008-5472.CAN-11-2507","article-title":"Urinary estrogens and estrogen metabolites and subsequent risk of breast cancer among premenopausal women","volume":"72","year":"2012","journal-title":"Cancer Res."},{"key":"2021112218022815000_BCJ-2019-0633C10","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1016\/j.steroids.2015.02.015","article-title":"Epidemiologic studies of estrogen metabolism and breast cancer","volume":"99","year":"2015","journal-title":"Steroids"},{"key":"2021112218022815000_BCJ-2019-0633C11","doi-asserted-by":"publisher","first-page":"150","DOI":"10.1016\/j.jsbmb.2006.12.102","article-title":"Estrogen metabolism and formation of estrogen-DNA adducts in estradiol-treated MCF-10F cells: the effects of 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin induction and catechol-O-methyltransferase inhibition","volume":"105","year":"2007","journal-title":"J. Steroid Biochem. Mol. Biol."},{"key":"2021112218022815000_BCJ-2019-0633C12","doi-asserted-by":"publisher","first-page":"1078","DOI":"10.1002\/ijc.30728","article-title":"Critical depurinating DNA adducts: estrogen adducts in the etiology and prevention of cancer and dopamine adducts in the etiology and prevention of Parkinson's disease","volume":"141","year":"2017","journal-title":"Int. J. Cancer"},{"key":"2021112218022815000_BCJ-2019-0633C13","doi-asserted-by":"publisher","first-page":"389","DOI":"10.1016\/j.neuroscience.2005.11.054","article-title":"Aromatase expression in the human temporal cortex","volume":"138","year":"2006","journal-title":"Neuroscience"},{"key":"2021112218022815000_BCJ-2019-0633C14","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1016\/j.brainres.2009.09.111","article-title":"Aromatase expression in the normal and epileptic human hippocampus","volume":"1315","year":"2010","journal-title":"Brain Res."},{"key":"2021112218022815000_BCJ-2019-0633C15","doi-asserted-by":"publisher","first-page":"705","DOI":"10.1111\/j.1365-2826.2008.01713.x","article-title":"Aromatase in the brain: not just for reproduction anymore","volume":"20","year":"2008","journal-title":"J. Neuroendocrinol."},{"key":"2021112218022815000_BCJ-2019-0633C16","doi-asserted-by":"publisher","first-page":"2562","DOI":"10.1210\/en.2011-2159","article-title":"Acute and specific modulation of presynaptic aromatization in the vertebrate brain","volume":"153","year":"2012","journal-title":"Endocrinology"},{"key":"2021112218022815000_BCJ-2019-0633C17","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1016\/j.tins.2006.03.004","article-title":"Is brain estradiol a hormone or a neurotransmitter?","volume":"29","year":"2006","journal-title":"Trends Neurosci."},{"key":"2021112218022815000_BCJ-2019-0633C18","doi-asserted-by":"publisher","first-page":"1177","DOI":"10.1111\/jnc.13513","article-title":"Region-specific rapid regulation of aromatase activity in zebra finch brain","volume":"136","year":"2016","journal-title":"J. Neurochem."},{"key":"2021112218022815000_BCJ-2019-0633C19","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1016\/j.yfrne.2015.01.001","article-title":"Sex differences and rapid estrogen signaling: a look at songbird audition","volume":"38","year":"2015","journal-title":"Front. Neuroendocrinol."},{"key":"2021112218022815000_BCJ-2019-0633C20","doi-asserted-by":"publisher","first-page":"219","DOI":"10.1016\/j.jphs.2016.06.005","article-title":"Ameliorative effect of membrane-associated estrogen receptor G protein coupled receptor 30 activation on object recognition memory in mouse models of Alzheimer's disease","volume":"131","year":"2016","journal-title":"J. Pharmacol. Sci."},{"key":"2021112218022815000_BCJ-2019-0633C21","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1016\/S0301-0082(03)00035-2","article-title":"Estrogens: protective or risk factors in brain function?","volume":"69","year":"2003","journal-title":"Prog. Neurobiol."},{"key":"2021112218022815000_BCJ-2019-0633C22","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1016\/j.neulet.2017.05.017","article-title":"Expression of aromatase and estrogen receptors in lumbar motoneurons of mice","volume":"653","year":"2017","journal-title":"Neurosci. Lett."},{"key":"2021112218022815000_BCJ-2019-0633C23","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1016\/j.mce.2013.12.018","article-title":"Brain sex matters: estrogen in cognition and Alzheimer's disease","volume":"389","year":"2014","journal-title":"Mol. Cell. Endocrinol."},{"key":"2021112218022815000_BCJ-2019-0633C24","doi-asserted-by":"publisher","first-page":"1364","DOI":"10.1007\/s12035-017-0400-2","article-title":"Estrogen attenuates local inflammasome expression and activation after spinal cord injury","volume":"55","year":"2017","journal-title":"Mol. Neurobiol."},{"key":"2021112218022815000_BCJ-2019-0633C25","doi-asserted-by":"publisher","first-page":"11181","DOI":"10.1523\/JNEUROSCI.1927-17.2017","article-title":"Plasticity of signaling by spinal estrogen receptor \u03b1, \u03ba-opioid receptor, and metabotropic glutamate receptors over the rat reproductive cycle regulates spinal endomorphin 2 antinociception: relevance of endogenous-biased agonism","volume":"37","year":"2017","journal-title":"J. Neurosci."},{"key":"2021112218022815000_BCJ-2019-0633C26","doi-asserted-by":"publisher","first-page":"e12561","DOI":"10.1111\/jne.12561","article-title":"Rapid non-genomic modulation by neurosteroids of dendritic spines in the hippocampus: androgen, estrogen and corticosteroid","volume":"30","year":"2017","journal-title":"J. Neuroendocrinol."},{"key":"2021112218022815000_BCJ-2019-0633C27","doi-asserted-by":"publisher","first-page":"507","DOI":"10.1007\/s00415-012-6665-5","article-title":"Endogenous female reproductive hormones and the risk of amyotrophic lateral sclerosis","volume":"260","year":"2013","journal-title":"J. Neurol."},{"key":"2021112218022815000_BCJ-2019-0633C28","doi-asserted-by":"publisher","first-page":"180","DOI":"10.1016\/j.brainresbull.2017.05.016","article-title":"Characterization of aromatase expression in the spinal cord of an animal model of familial ALS","volume":"132","year":"2017","journal-title":"Brain Res. Bull."},{"key":"2021112218022815000_BCJ-2019-0633C29","doi-asserted-by":"publisher","first-page":"1283","DOI":"10.1212\/WNL.0000000000004390","article-title":"A case-control study of hormonal exposures as etiologic factors for ALS in women Euro-MOTOR","volume":"89","year":"2017","journal-title":"Neurology."},{"key":"2021112218022815000_BCJ-2019-0633C30","doi-asserted-by":"publisher","first-page":"e12917","DOI":"10.7554\/eLife.12917","article-title":"Acute inhibition of neurosteroid estrogen synthesis suppresses status epilepticus in an animal model","volume":"5","year":"2016","journal-title":"eLife"},{"key":"2021112218022815000_BCJ-2019-0633C31","doi-asserted-by":"publisher","first-page":"1634","DOI":"10.1210\/me.2009-0039","article-title":"Rapid estradiol\/ERalpha signaling enhances aromatase enzymatic activity in breast cancer cells","volume":"23","year":"2009","journal-title":"Mol. Endocrinol."},{"key":"2021112218022815000_BCJ-2019-0633C32","doi-asserted-by":"publisher","first-page":"5157","DOI":"10.1210\/en.2012-1561","article-title":"Estrogens and PTP1B function in a novel pathway to regulate aromatase enzymatic activity in breast cancer cells","volume":"153","year":"2012","journal-title":"Endocrinology"},{"key":"2021112218022815000_BCJ-2019-0633C33","doi-asserted-by":"publisher","first-page":"4830","DOI":"10.1111\/febs.13021","article-title":"Post-translational dual regulation of cytochrome P450 aromatase at the catalytic and protein levels by phosphorylation\/dephosphorylation","volume":"281","year":"2014","journal-title":"FEBS J."},{"key":"2021112218022815000_BCJ-2019-0633C34","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1016\/j.jsbmb.2008.09.001","article-title":"Aromatase is phosphorylated in situ at serine-118","volume":"112","year":"2008","journal-title":"J. Steroid Biochem. Mol. Biol."},{"key":"2021112218022815000_BCJ-2019-0633C35","doi-asserted-by":"publisher","first-page":"219","DOI":"10.1038\/nature07614","article-title":"Structural basis for androgen specificity and oestrogen synthesis in human aromatase","volume":"457","year":"2009","journal-title":"Nature"},{"key":"2021112218022815000_BCJ-2019-0633C36","doi-asserted-by":"publisher","first-page":"5821","DOI":"10.1021\/bi400669h","article-title":"Structural basis for the functional roles of critical residues in human cytochrome p450 aromatase","volume":"52","year":"2013","journal-title":"Biochemistry"},{"key":"2021112218022815000_BCJ-2019-0633C37","doi-asserted-by":"publisher","first-page":"8464","DOI":"10.1021\/jm300930n","article-title":"Novel aromatase inhibitors by structure-guided design","volume":"55","year":"2012","journal-title":"J. Med. Chem."},{"key":"2021112218022815000_BCJ-2019-0633C38","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1016\/j.jsbmb.2009.09.012","article-title":"X-ray structure of human aromatase reveals an androgen-specific active site","volume":"118","year":"2010","journal-title":"J. Steroid Biochem. Mol. Biol."},{"key":"2021112218022815000_BCJ-2019-0633C39","doi-asserted-by":"publisher","first-page":"1186","DOI":"10.1074\/jbc.M114.595108","article-title":"Evidence for an elevated aspartate pKa in the active site of human aromatase","volume":"290","year":"2015","journal-title":"J. Biol. Chem."},{"key":"2021112218022815000_BCJ-2019-0633C40","doi-asserted-by":"publisher","first-page":"4622","DOI":"10.1210\/en.2014-1561","article-title":"Mechanism of inhibition of estrogen biosynthesis by azole fungicides","volume":"155","year":"2014","journal-title":"Endocrinology"},{"key":"2021112218022815000_BCJ-2019-0633C41","doi-asserted-by":"publisher","first-page":"5131","DOI":"10.1021\/acs.jmedchem.5b01281","article-title":"Recent progress in the discovery of next generation inhibitors of aromatase from the structure-function perspective","volume":"59","year":"2016","journal-title":"J. Med. Chem."},{"key":"2021112218022815000_BCJ-2019-0633C42","doi-asserted-by":"publisher","first-page":"e32565","DOI":"10.1371\/journal.pone.0032565","article-title":"Motion and flexibility in human cytochrome P450 aromatase","volume":"7","year":"2012","journal-title":"PLoS ONE"},{"key":"2021112218022815000_BCJ-2019-0633C43","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1007\/978-3-319-17972-8","volume-title":"Resistance to Aromatase Inhibitors in Breast Cancer","author":"Larionov","year":"2015"},{"key":"2021112218022815000_BCJ-2019-0633C44","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1016\/j.jsbmb.2018.02.009","article-title":"Testosterone complex and non-steroidal ligands of human aromatase","volume":"181","year":"2018","journal-title":"J. Steroid Biochem. Mol. Biol."},{"key":"2021112218022815000_BCJ-2019-0633C45","doi-asserted-by":"publisher","first-page":"3003","DOI":"10.1021\/bi00226a004","article-title":"Purification of human placental aromatase cytochrome P-450 with monoclonal antibody and its characterization","volume":"30","year":"1991","journal-title":"Biochemistry"},{"key":"2021112218022815000_BCJ-2019-0633C46","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1016\/j.jsbmb.2003.12.010","article-title":"Suppression of human cytochrome P450 aromatase activity by monoclonal and recombinant antibody fragments and identification of a stable antigenic complex","volume":"88","year":"2004","journal-title":"J. Steroid Biochem. Mol. Biol."},{"key":"2021112218022815000_BCJ-2019-0633C47","doi-asserted-by":"publisher","first-page":"174","DOI":"10.1016\/j.mce.2008.09.029","article-title":"Structural basis for the selective inhibition of human 3\u03b2-hydroxysteroid dehydrogenase 1 in human breast tumor MCF-7 cells","volume":"301","year":"2009","journal-title":"Mol. Cell. Endocrinol."},{"key":"2021112218022815000_BCJ-2019-0633C48","first-page":"6949","article-title":"Stable expression of human aromatase complementary DNA in mammalian cells: a useful system for aromatase inhibitor screening","volume":"50","year":"1990","journal-title":"Cancer Res."},{"key":"2021112218022815000_BCJ-2019-0633C49","first-page":"5092","article-title":"A new nude mouse model for postmenopausal breast cancer using MCF-7 cells transfected with the human aromatase gene","volume":"54","year":"1994","journal-title":"Cancer Res."},{"key":"2021112218022815000_BCJ-2019-0633C50","doi-asserted-by":"publisher","first-page":"1605","DOI":"10.1002\/jcc.20084","article-title":"UCSF chimera\u2013a visualization system for exploratory research and analysis","volume":"25","year":"2004","journal-title":"J. Comput. Chem."},{"key":"2021112218022815000_BCJ-2019-0633C51","doi-asserted-by":"publisher","first-page":"1397","DOI":"10.5012\/bkcs.2010.31.5.1397","article-title":"Refined structure of human NM23-H1 from a hexagonal crystal","volume":"31","year":"2010","journal-title":"Bull. Korean Chem. Soc."},{"key":"2021112218022815000_BCJ-2019-0633C52","doi-asserted-by":"publisher","first-page":"261","DOI":"10.1007\/s10863-006-9043-0","article-title":"Crystal structures of S120G mutant and wild type of human nucleoside diphosphate kinase A in complex with ADP","volume":"38","year":"2006","journal-title":"J. Bioenerg. Biomembr."},{"key":"2021112218022815000_BCJ-2019-0633C53","doi-asserted-by":"publisher","first-page":"11062","DOI":"10.1021\/bi00035a011","article-title":"Mechanism of phosphate transfer by nucleoside diphosphate kinase: X-ray structures of the phosphohistidine intermediate of the enzymes from Drosophila and Dictyostelium","volume":"34","year":"1995","journal-title":"Biochemistry"},{"key":"2021112218022815000_BCJ-2019-0633C54","doi-asserted-by":"publisher","first-page":"3258","DOI":"10.1038\/ncomms4258","article-title":"Visualizing autophosphorylation in histidine kinases","volume":"5","year":"2014","journal-title":"Nat. Commun."},{"key":"2021112218022815000_BCJ-2019-0633C55","doi-asserted-by":"publisher","first-page":"198","DOI":"10.1016\/j.cell.2015.05.046","article-title":"Monoclonal 1-and 3-phosphohistidine antibodies: new tools to study histidine phosphorylation","volume":"162","year":"2015","journal-title":"Cell"},{"key":"2021112218022815000_BCJ-2019-0633C56","doi-asserted-by":"publisher","first-page":"308","DOI":"10.1006\/abbi.1996.0395","article-title":"The interaction of NADPH-P450 reductase with P450: an electrochemical study of the role of the flavin mononucleotide-binding domain","volume":"333","year":"1996","journal-title":"Arch. Biochem. Biophys."},{"key":"2021112218022815000_BCJ-2019-0633C57","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1016\/j.jsbmb.2009.11.010","article-title":"Sequence-function correlation of aromatase and its interaction with reductase","volume":"118","year":"2010","journal-title":"J. Steroid Biochem. Mol. Biol."},{"key":"2021112218022815000_BCJ-2019-0633C58","unstructured":"Koivum\u00e4ki, T. (2018) Whey protein oxidation: LC\u2013MS investigations of peptide markers"},{"key":"2021112218022815000_BCJ-2019-0633C59","doi-asserted-by":"publisher","first-page":"1053","DOI":"10.1007\/s00726-010-0715-z","article-title":"Proline and hydroxyproline metabolism: implications for animal and human nutrition","volume":"40","year":"2011","journal-title":"Amino Acids"},{"key":"2021112218022815000_BCJ-2019-0633C60","doi-asserted-by":"publisher","first-page":"378","DOI":"10.3390\/biom5020378","article-title":"Mass spectrometry-based methods for identifying oxidized proteins in disease: advances and challenges","volume":"5","year":"2015","journal-title":"Biomolecules"},{"key":"2021112218022815000_BCJ-2019-0633C61","doi-asserted-by":"publisher","first-page":"26482","DOI":"10.1074\/jbc.M109.009340","article-title":"Unraveling delta1-pyrroline-5-carboxylate (P5C)\/proline cycle in plants by uncoupled expression of proline oxidation enzymes","volume":"284","year":"2009","journal-title":"J. Biol. Chem."},{"key":"2021112218022815000_BCJ-2019-0633C62","doi-asserted-by":"publisher","first-page":"3244","DOI":"10.1039\/c3cs60432b","article-title":"Advances in radical probe mass spectrometry for protein footprinting in chemical biology applications","volume":"43","year":"2014","journal-title":"Chem. Soc Rev."},{"key":"2021112218022815000_BCJ-2019-0633C63","doi-asserted-by":"publisher","first-page":"2930","DOI":"10.1021\/acs.jcim.9b00157","article-title":"The post-translational regulation of CYP450s metabolism as revealed by all-atoms simulations of the aromatase enzyme","volume":"59","year":"2019","journal-title":"J. Chem. Inform. Model."},{"key":"2021112218022815000_BCJ-2019-0633C64","unstructured":"Technology CS. PhosphoSitePlus [https:\/\/www.phosphosite.org\/proteinAction.action?id=18992&showAllSites=true]"},{"key":"2021112218022815000_BCJ-2019-0633C65","doi-asserted-by":"publisher","first-page":"1285","DOI":"10.1038\/nbt1240","article-title":"A probability-based approach for high-throughput protein phosphorylation analysis and site localization","volume":"24","year":"2006","journal-title":"Nat. Biotechnol."},{"key":"2021112218022815000_BCJ-2019-0633C66","doi-asserted-by":"publisher","first-page":"243","DOI":"10.1046\/j.1432-1033.2001.01886.x","article-title":"Evaluation of the mechanism of aromatase cytochrome P450: A site-directed mutagenesis study","volume":"268","year":"2001","journal-title":"Eur. J. Biochem."},{"key":"2021112218022815000_BCJ-2019-0633C67","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1016\/j.ceb.2016.12.010","article-title":"Phisphorylation: the emergence of histidine phosphorylation as a reversible regulatory modification","volume":"45","year":"2017","journal-title":"Curr. Opin. Cell Biol."},{"key":"2021112218022815000_BCJ-2019-0633C68","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1038\/nmeth.4580","article-title":"Widespread bacterial protein histidine phosphorylation revealed by mass spectrometry-based proteomics","volume":"15","year":"2018","journal-title":"Nat. Methods"},{"key":"2021112218022815000_BCJ-2019-0633C69","doi-asserted-by":"publisher","first-page":"202820","DOI":"10.1101\/202820","article-title":"Extensive non-canonical phosphorylation in human cells revealed using strong-anion exchange-mediated phosphoproteomics","year":"2017","journal-title":"BioRxiv"},{"key":"2021112218022815000_BCJ-2019-0633C70","doi-asserted-by":"publisher","first-page":"498","DOI":"10.1016\/0006-291X(89)92025-1","article-title":"Placental estrogen synthetase (aromatase): evidence for phosphatase-dependent inactivation","volume":"162","year":"1989","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"2021112218022815000_BCJ-2019-0633C71","doi-asserted-by":"publisher","first-page":"949","DOI":"10.1002\/jms.1974","article-title":"Modelling of the gas-phase phosphate group loss and rearrangement in phosphorylated peptides","volume":"46","year":"2011","journal-title":"J. Mass Spectrom."},{"key":"2021112218022815000_BCJ-2019-0633C72","volume-title":"Resistance to Aromatase Inhibitors in Breast Cancer","year":"2015"},{"key":"2021112218022815000_BCJ-2019-0633C73","doi-asserted-by":"publisher","first-page":"201","DOI":"10.1186\/bcr2931","article-title":"Understanding the mechanisms of aromatase inhibitor resistance","volume":"14","year":"2012","journal-title":"Breast Cancer Res."},{"key":"2021112218022815000_BCJ-2019-0633C74","doi-asserted-by":"publisher","first-page":"261","DOI":"10.1038\/nrc3920","article-title":"Mechanisms of aromatase inhibitor resistance","volume":"15","year":"2015","journal-title":"Nat. Rev. Cancer"},{"key":"2021112218022815000_BCJ-2019-0633C75","first-page":"87","article-title":"Ineffective Inhibition of Aromatase: A Cause for AI Resistance?","author":"Larionov","year":"2015","journal-title":"Resistance to Aromatase Inhibitors in Breast Cancer"},{"key":"2021112218022815000_BCJ-2019-0633C76","doi-asserted-by":"publisher","first-page":"444","DOI":"10.1038\/ng.3773","article-title":"Acquired CYP19A1 amplification is an early specific mechanism of aromatase inhibitor resistance in ER\u03b1 metastatic breast cancer","volume":"49","year":"2017","journal-title":"Nat. Genet."}],"container-title":["Biochemical Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/portlandpress.com\/biochemj\/article-pdf\/476\/21\/3313\/859940\/bcj-2019-0633.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/portlandpress.com\/biochemj\/article-pdf\/476\/21\/3313\/859940\/bcj-2019-0633.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,21]],"date-time":"2023-09-21T13:09:34Z","timestamp":1695301774000},"score":1,"resource":{"primary":{"URL":"https:\/\/portlandpress.com\/biochemj\/article\/476\/21\/3313\/220764\/Phosphorylation-of-human-placental-aromatase"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,11,11]]},"references-count":76,"journal-issue":{"issue":"21","published-print":{"date-parts":[[2019,11,15]]}},"URL":"https:\/\/doi.org\/10.1042\/bcj20190633","relation":{},"ISSN":["0264-6021","1470-8728"],"issn-type":[{"value":"0264-6021","type":"print"},{"value":"1470-8728","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,11,11]]}}}