Melatonin, an endogenous-specific inhibitor of estrogen receptor alpha via calmodulin

The Journal of Biological Chemistry
Beatriz del RíoS Ramos

Abstract

Melatonin is an indole hormone produced mainly by the pineal gland. We have previously demonstrated that melatonin interferes with estrogen (E(2)) signaling in MCF7 cells by impairing estrogen receptor (ER) pathways. Here we present the characterization of its mechanism of action showing that melatonin is a specific inhibitor of E(2)-induced ERalpha-mediated transcription in both estrogen response element- and AP1-containing promoters, whereas ERbeta-mediated transactivation is not inhibited or even activated at certain promoters. We show that the sensitivity of MCF-7 cells to melatonin depends on the ERalpha/ERbeta ratio, and ectopic expression of ERbeta results in MCF-7 cells becoming insensitive to this hormone. Melatonin acts as a calmodulin antagonist inducing conformational changes in the ERalpha-calmodulin (CaM) complex, thus impairing the binding of E(2).ERalpha.CaM complex to DNA and, therefore, preventing ERalpha-dependent transcription. Moreover the mutant ERalpha (K302G,K303G), unable to bind calmodulin, becomes insensitive to melatonin. The effect of melatonin is specific since other related indoles neither interact with CaM nor inhibit ERalpha-mediated transactivation. Interestingly, melatonin does not affect the ...Continue Reading

References

Jan 1, 1992·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·M P Coleman, R J Reiter
Feb 1, 1988·Molecular Endocrinology·G CastoriaF Auricchio
Mar 17, 1995·Biochemical and Biophysical Research Communications·A Bouhoute, G Leclercq
Oct 11, 1994·Proceedings of the National Academy of Sciences of the United States of America·V CavaillèsM G Parker
Sep 17, 1996·Proceedings of the National Academy of Sciences of the United States of America·E M McInerneyB S Katzenellenbogen
Dec 1, 1996·Endocrine Reviews·M Beato, A Sánchez-Pacheco
Oct 24, 1997·Nature·A M BrzozowskiM Carlquist
Oct 8, 1998·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·M P RomeroC Osuna
May 4, 1999·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·A G RatoS Ramos
Feb 16, 2000·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·P LissoniG Tancini
May 24, 2000·The Journal of Steroid Biochemistry and Molecular Biology·C J NewtonS L Atkin
Mar 30, 2001·The Journal of Biological Chemistry·Z LiD B Sacks
Oct 18, 2001·Journal of the National Cancer Institute·E S SchernhammerG A Colditz
May 1, 2002·Molecular Endocrinology·Juana M García PedreroSofía Ramos
Jun 5, 2003·Journal of the National Cancer Institute·Eva S SchernhammerGraham A Colditz

❮ Previous
Next ❯

Citations

Dec 4, 2009·Der Hautarzt; Zeitschrift für Dermatologie, Venerologie, und verwandte Gebiete·T W Fischer
Jun 2, 2007·Breast Cancer Research and Treatment·V SrinivasanG J Maestroni
Jul 2, 2008·Breast Cancer Research and Treatment·Ahmet KorkmazRussel J Reiter
Jul 21, 2011·Journal of Mammary Gland Biology and Neoplasia·Steven M HillTamika Duplesis
Feb 6, 2009·Expert Reviews in Molecular Medicine·Stephen G GrantPaula A Witt-Enderby
May 9, 2012·The Journal of Endocrinology·Melyssa R BrattonMatthew E Burow
Apr 2, 2014·Frontiers in Neuroendocrinology·Sarah A LaredoBrian C Trainor
Oct 25, 2006·Breast Cancer Research and Treatment·James B BurchRobert L Wells
Sep 26, 2012·Cellular and Molecular Life Sciences : CMLS·Sara ProiettiMariano Bizzarri
Sep 10, 2005·Journal of Pineal Research·Sylvia AustTheresia Thalhammer
Dec 15, 2007·Journal of Pineal Research·Tobias W FischerRalf Paus
Feb 27, 2008·Journal of Pineal Research·A GonzalezE J Sanchez-Barcelo
Aug 2, 2006·Journal of Pineal Research·Guillermo García-SantosCarmen Rodriguez
Oct 31, 2014·Journal of Animal Physiology and Animal Nutrition·K L KappenK S Swanson
Mar 28, 2016·Breast Cancer : the Journal of the Japanese Breast Cancer Society·Elaheh NooshinfarMohammad Esmaeil Akbari
Aug 1, 2015·Cancer Causes & Control : CCC·Elizabeth M PooleShelley S Tworoger
Sep 20, 2011·Free Radical Research·Ana M Sánchez-SánchezCarmen Rodriguez
Apr 17, 2015·Endocrine-related Cancer·Steven M HillDavid E Blask
Apr 20, 2017·International Journal of Molecular Sciences·Russel J ReiterKexin Xu
Aug 29, 2006·The American Journal of Pathology·Domenico AlvaroEugenio Gaudio
Sep 26, 2008·Integrative Cancer Therapies·Venkataramanujan SrinivasanDaniel P Cardinali
Jan 6, 2010·Integrative Cancer Therapies·Steven M HillLulu Mao
Sep 8, 2017·International Journal of Molecular Sciences·Federica Lo SardoSabrina Strano
Sep 24, 2015·Physical Chemistry Chemical Physics : PCCP·Haochen Ke, James M Lisy
Oct 17, 2018·Asian Spine Journal·Shu-Yan NgKaren Kar Yin Chan
Sep 7, 2012·Reproduction, Fertility, and Development·Kenichiro SakaguchiBunpei Ishizuka
Apr 9, 2005·Journal of Pineal Research·Emilio J Sánchez-BarcelóCarolina Alonso-González
May 17, 2008·Journal of Pineal Research·Leonardo Ortíz-LópezGloria Benítez-King
Jul 23, 2008·Experimental Dermatology·Tobias W FischerRalf Paus
Apr 26, 2006·Journal of Pineal Research·C Martínez-CampaE J Sánchez-Barceló
Jun 14, 2006·The Journal of Biological Chemistry·Juana M García-PedreroBorja Belandia
Jun 11, 2010·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Francesca LuchettiFrancesco Galli
Jul 2, 2011·Journal of Pineal Research·Alicia GonzálezSamuel Cos
Jul 24, 2015·Molecular Nutrition & Food Research·Jon MerlinDana S Hutchinson
Dec 14, 2011·Journal of Pineal Research·Virginia Alvarez-GarcíaSamuel Cos
Jun 11, 2020·Archives of Physiology and Biochemistry·Saptadip Samanta

❮ Previous
Next ❯

Related Concepts

Related Feeds

ASBMB Publications

The American Society for Biochemistry and Molecular Biology (ASBMB) includes the Journal of Biological Chemistry, Molecular & Cellular Proteomics, and the Journal of Lipid Research. Discover the latest research from ASBMB here.