Etoposide-induced protein 2.4 functions as a regulator of the calcium ATPase and protects pancreatic β-cell survival

The Journal of Biological Chemistry
Lin YuanPingyong Xu

Abstract

Calcium homeostasis is essential for maintaining the viability and function of pancreatic β cells and plays a key role in preventing the development of diabetes. Decreased levels of ATPase sarcoplasmic/endoplasmic reticulum Ca2+-transporting 2 (ATP2a2), the main calcium pump in β cells, are often found in individuals with diabetes and in diabetic animal models. However, the regulators of ATP2a2 and the molecular mechanisms responsible for controlling ATP2a2 activity remain unclear. Etoposide-induced protein 2.4 (Ei24) is also down-regulated in β cells of diabetic individuals, whereas the effect of decreased Ei24 level on β-cell function is not clarified. Here, using Cre-LoxP and CRISPR/Cas9-based genomic knockout (KO) approaches to generate pancreatic β cell-specific Ei24 KO mice and pancreatic β-cell lines, we found that Ei24 regulates ATP2a2 activity. Specifically, we observed that Ei24 binds to ATP2a2 through Ei24 residues 293-299, which we named here the ATP2a2-interacting region (AIR). Loss of Ei24 inactivated ATP2a2, disrupted calcium homeostasis, and deactivated the calcium/calmodulin-dependent protein kinase kinase 2 (CAMKK2)-AMP-activated protein kinase (AMPK) pathway. Elevation of calcium concentration in the endoplas...Continue Reading

References

Dec 14, 1999·Molecular and Cellular Biology·Z GuG P Zambetti
Mar 25, 2005·Diabetic Medicine : a Journal of the British Diabetic Association·D A Rees, J C Alcolado
Nov 6, 2007·FEBS Letters·Christina N MorkRemco A Spanjaard
Feb 7, 2009·The EMBO Journal·Griselda Herrero-MartínMarja Jäättelä
Mar 11, 2010·Advances in Experimental Medicine and Biology·James D Johnson, Dan S Luciani
Sep 9, 2010·Genesis : the Journal of Genetics and Development·Junghun SongQingchun Tong
Mar 29, 2011·Cold Spring Harbor Perspectives in Biology·Ilse VandecaetsbeekJo Vanoevelen
Jul 10, 2012·The International Journal of Biochemistry & Cell Biology·Sushil DevkotaHan-Woong Lee
Oct 18, 2012·The Journal of Biological Chemistry·Yan G ZhaoHong Zhang
Oct 2, 2014·Cell Calcium·Angel Zarain-HerzbergRafael Estrada-Avilés
May 27, 2016·The Journal of Biological Chemistry·Ananthalakshmy SundararamanAnnapoorni Rangarajan
Aug 11, 2017·Cell & Bioscience·Kai YuanJiang-Feng Wu

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Citations

Jul 25, 2019·Cellular and Molecular Life Sciences : CMLS·Lin YuanPingyong Xu
Aug 10, 2019·Frontiers in Oncology·Mihwa HwangSunshin Kim
Dec 31, 2020·International Journal of Molecular Sciences·Rizwan QaisarHolly Van Remmen
Dec 29, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Yanwen MaoBing Guo

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