Transcriptional regulation of APH-1A and increased gamma-secretase cleavage of APP and Notch by HIF-1 and hypoxia

FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology
Ruishan WangHuaxi Xu

Abstract

The proteolytic cleavage of Alzheimer beta-amyloid precursor protein (APP) and signaling receptor Notch is mediated by the PS/gamma-secretase complex, which consists of presenilins, nicastrin, APH-1, and PEN-2. Although the four components are known to coordinately regulate each other at the protein level, information regarding their transcription regulation is scarce. Here we characterized the 5'-flanking region of the human APH-1A gene and identified a 271-bp fragment containing the transcription initiation site for the promoter activity. Sequence analysis, mutagenesis, and gel shift studies revealed a binding of AP4 and HIF-1 to the promoter, which affects the promoter activity. Activation of HIF-1 by short-term NiCl2 treatments (a condition of chemical hypoxia) dramatically increased APH-1A mRNA and protein expression, accompanied by increased secretion of Abeta and decreased APP CTFs formation, indicative of an increase in gamma-secretase activity. NiCl2 treatments had little effect on APP and the other three components of the gamma-secretase complex. The cellular concentration of Notch intracellular domain (NICD) was also increased by the hypoxic treatment. Our results demonstrate that APH-1A expression and the gamma-secr...Continue Reading

References

Jul 1, 1992·Proceedings of the National Academy of Sciences of the United States of America·S S Sisodia
Apr 30, 1996·Proceedings of the National Academy of Sciences of the United States of America·H XuS Gandy
Jun 9, 1999·Proceedings of the National Academy of Sciences of the United States of America·W SongB A Yankner
Jun 12, 1999·American Journal of Human Genetics·S S SisodiaG Thinakaran
Nov 11, 1999·Genes & Development·D B DonovielA Bernstein
Mar 7, 2000·Frontiers in Bioscience : a Journal and Virtual Library·J P GreenfieldH Xu
Dec 26, 2000·The Journal of Biological Chemistry·N MitsudaM Tohyama
Jan 17, 2002·Proceedings of the National Academy of Sciences of the United States of America·Caroline GoutteJames R Priess
Feb 2, 2002·The Journal of Biological Chemistry·Jeffrey P GreenfieldHuaxi Xu
Apr 12, 2002·The Journal of Biological Chemistry·Jae Yoon LeemGopal Thinakaran
May 16, 2002·Proceedings of the National Academy of Sciences of the United States of America·Annika JögiSven Påhlman
May 29, 2002·The Journal of Biological Chemistry·Dun-Sheng YangPaul E Fraser
Nov 20, 2002·Annals of the New York Academy of Sciences·Karen SetaDavid E Millhorn
Jan 11, 2003·The Journal of Biological Chemistry·Wen-jie LuoHuaxi Xu
May 13, 2003·Proceedings of the National Academy of Sciences of the United States of America·W Taylor KimberlyDennis J Selkoe
Jun 20, 2003·The Journal of Biological Chemistry·Jinhe LiJeffrey S Nye
Jan 1, 2004·Molecular and Cellular Biology·Michelle A ChristensenWeihong Song
Jan 17, 2004·Cancer Biology & Therapy·Patrick Maxwell, Konstantin Salnikow
Jun 15, 2004·Current Opinion in Neurobiology·Takeshi Iwatsubo
Aug 3, 2004·The Journal of Biological Chemistry·Keiro ShirotaniHarald Steiner
Aug 12, 2004·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Gopal Thinakaran, Angèle T Parent
Aug 13, 2004·Brain Research. Molecular Brain Research·Margaret J SmithJanetta G Culvenor
Nov 26, 2004·Proceedings of the National Academy of Sciences of the United States of America·Leonid TarassishinYue-Ming Li
Jan 7, 2005·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Guojun MaPhilip C Wong
Apr 13, 2005·Biochemical and Biophysical Research Communications·Shinya SaitoWataru Araki
Jul 13, 2005·Mutation Research·Max CostaThomas Kluz
Nov 1, 2005·Developmental Cell·Maria V GustafssonMaria Bondesson

❮ Previous
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Citations

Oct 29, 2010·Journal of Molecular Neuroscience : MN·Alessio CrestiniAnnamaria Confaloni
Feb 22, 2011·Medical Oncology·Liu XinghuaChen Jianying
Oct 12, 2012·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Ben-Shun HuJing-Wang Tan
Feb 21, 2008·Nature Reviews. Molecular Cell Biology·M Celeste Simon, Brian Keith
Jan 26, 2011·Proceedings of the National Academy of Sciences of the United States of America·Dan ZhouGabriel G Haddad
Nov 6, 2009·Journal of Cell Science·Julie DunysCristine Alves da Costa
May 5, 2011·PloS One·Jordan T NewingtonRobert C Cumming
Feb 8, 2011·Journal of Clinical Biochemistry and Nutrition·Ken ShiratoNaoyuki Taniguchi
Mar 22, 2014·Translational Neurodegeneration·Hui Liu, Weidong Le
Oct 16, 2009·Journal of Bioenergetics and Biomembranes·Cristina CarvalhoGeorge Perry
Sep 19, 2009·Cellular and Molecular Life Sciences : CMLS·O O Ogunshola, X Antoniou
Oct 9, 2013·Critical Reviews in Biochemistry and Molecular Biology·Veronica L DenglerJoaquín M Espinosa
Aug 30, 2008·Physiological and Biochemical Zoology : PBZ·Shana R Lavin, William H Karasov
Sep 25, 2007·Biochemical and Biophysical Research Communications·Hiroki HayashiYasufumi Kaneda
Feb 10, 2018·Evidence-based Complementary and Alternative Medicine : ECAM·Meixia LiuHao Li
Feb 7, 2009·Journal of Neurochemistry·Michela GuglielmottoMassimo Tabaton
May 9, 2012·The EMBO Journal·Samantha N GreerMichael Ohh
Feb 23, 2012·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Hiroki HayashiYasufumi Kaneda
Jun 4, 2015·Molecular and Cellular Biochemistry·Shaopeng Chen, Sung-Kay Chiu
Mar 18, 2017·The Journal of Biological Chemistry·Kota FujikiMasato Matsuoka
Mar 19, 2020·Science Signaling·Sunmin JungYong-Keun Jung
Feb 23, 2021·Journal of Alzheimer's Disease : JAD·Yang-Yang WangZhi-You Cai
May 1, 2017·Experimental Cell Research·Sebastian K-J Landor, Urban Lendahl
May 14, 2017·Biochimica Et Biophysica Acta. General Subjects·Safiyeh Aghazadeh, Razieh Yazdanparast

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