Transcriptional Regulation of X-Box-binding Protein One (XBP1) by Hepatocyte Nuclear Factor 4α (HNF4Α) Is Vital to Beta-cell Function.

The Journal of Biological Chemistry
Benjamin D MooreJason C Mills

Abstract

The transcription factor, X-box-binding protein-1 (XBP1), controls the development and maintenance of the endoplasmic reticulum (ER) in multiple secretory cell lineages. We show here that Hepatocyte Nuclear Factor 4α (HNF4α) directly induces XBP1 expression. Mutations in HNF4α cause Mature-Onset Diabetes of the Young I (MODYI), a subset of diabetes characterized by diminished GSIS. In mouse models, cell lines, and ex vivo islets, using dominant negative and human- disease-allele point mutants or knock-out and knockdown models, we show that disruption of HNF4α caused decreased expression of XBP1 and reduced cellular ER networks. GSIS depends on ER Ca(2+) signaling; we show that diminished XBP1 and/or HNF4α in β-cells led to impaired ER Ca(2+) homeostasis. Restoring XBP1 expression was sufficient to completely rescue GSIS in HNF4α-deficient β-cells. Our findings uncover a transcriptional relationship between HNF4α and Xbp1 with potentially broader implications about MODYI and the importance of transcription factor signaling in the regulation of secretion.

References

Jan 1, 1996·Cell Calcium·A Verkhratsky, A Shmigol
Apr 10, 1995·Physical Review Letters·M S AlamR Mountain
Oct 16, 2003·Molecular and Cellular Biology·Ann-Hwee LeeLaurie H Glimcher
Mar 11, 2004·Genes to Cells : Devoted to Molecular & Cellular Mechanisms·Naoki Ogawa, Kazutoshi Mori
Jun 3, 2004·Methods in Molecular Biology·Hogune ImEmery H Bresnick
Aug 18, 2004·PLoS Biology·Jess H LeberPeter Walter
Dec 9, 2004·Proceedings of the National Academy of Sciences of the United States of America·Amy E PalmerRoger Y Tsien
Mar 29, 2005·Diabetes·Allison M BagwellDonald W Bowden
Dec 20, 2005·The EMBO Journal·Ann-Hwee LeeLaurie H Glimcher
Dec 27, 2005·The Journal of Biological Chemistry·Atsuko MiuraIichiro Shimomura
May 23, 2006·Proceedings of the National Academy of Sciences of the United States of America·Michele A BattleStephen A Duncan
Jun 17, 2008·Science·Ann-Hwee LeeLaurie H Glimcher
Aug 16, 2008·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Jennifer Luebke-WheelerStephen A Duncan
Mar 27, 2009·The Journal of Biological Chemistry·Mary E B MartinoCarla M P Ribeiro
Jun 9, 2009·Methods in Molecular Biology·Anna L Nolan, Jacqueline F O'Dowd
Aug 28, 2009·The Journal of Pharmacology and Experimental Therapeutics·Sarah Melissa P JacoboGregory H Hockerman
Sep 16, 2009·The Journal of Experimental Medicine·Derrick J ToddLaurie H Glimcher
Sep 19, 2009·BMC Gastroenterology·Mette BoydJesper T Troelsen
Sep 19, 2009·Methods in Molecular Biology·Latha Muniappan, Sabire Ozcan
Oct 31, 2009·Nature Protocols·Dong-Sheng LiLong-Jun Dai
Dec 30, 2009·Molecular and Cellular Biology·Xiaolin TianJason C Mills
Jan 8, 2010·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Eugene BolotinFrances M Sladek
Oct 27, 2010·Proceedings of the National Academy of Sciences of the United States of America·Sang Won ParkUmut Ozcan
Jan 27, 2011·Methods in Enzymology·Christine M Oslowski, Fumihiko Urano
May 11, 2011·Proceedings of the National Academy of Sciences of the United States of America·Ann-Hwee LeeLaurie H Glimcher
Oct 27, 2011·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Jason C Mills, Paul H Taghert
Jan 14, 2012·The Journal of Biological Chemistry·Jessica A BonzoFrank J Gonzalez

❮ Previous
Next ❯

Citations

Jun 25, 2016·American Journal of Physiology. Gastrointestinal and Liver Physiology·Benjamin D MooreJason C Mills
Aug 23, 2019·World Journal of Gastroenterology : WJG·Matthew M YehSayed S Daoud
Mar 12, 2020·Environmental Science. Processes & Impacts·Sheri ChenRaymond B Runyan
Aug 14, 2020·The Journal of Biological Chemistry·Rohit B SharmaLaura C Alonso
Jan 7, 2018·Toxicology Letters·Alondra P HarrisRaymond B Runyan
May 19, 2020·Molecular and Cellular Endocrinology·Minyi ZhangMin Guan
Aug 7, 2021·Biomedicines·Sung-Min ParkJae-Seon So

❮ 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.

Calcium & Bioenergetics

Bioenergetic processes, including cellular respiration and photosynthesis, concern the transformation of energy by cells. Here is the latest research on the role of calcium in bioenergetics.