Native and Polyubiquitinated Forms of Dihydroceramide Desaturase Are Differentially Linked to Human Embryonic Kidney Cell Survival

Molecular and Cellular Biology
Mariam AlsanafiNigel J Pyne

Abstract

There is controversy concerning the role of dihydroceramide desaturase (Degs1) in regulating cell survival, with studies showing that it can both promote and protect against apoptosis. We have therefore investigated the molecular basis for these opposing roles of Degs1. Treatment of HEK293T cells with the sphingosine kinase inhibitor SKi [2-(p-hydroxyanilino)-4-(p-chlorophenyl)thiazole] or fenretinide, but not the Degs1 inhibitor GT11 {N-[(1R,2S)-2-hydroxy-1-hydroxymethyl-2-(2-tridecyl-1-cyclopropenyl)ethyl]octan-amide}, induced the polyubiquitination of Degs1 (Mr = 40 to 140 kDa) via a mechanism involving oxidative stress, p38 mitogen-activated protein kinase (MAPK), and Mdm2 (E3 ligase). The polyubiquitinated forms of Degs1 exhibit "gain of function" and activate prosurvival pathways, p38 MAPK, c-Jun N-terminal kinase (JNK), and X-box protein 1s (XBP-1s). In contrast, another sphingosine kinase inhibitor, ABC294640 [3-(4-chlorophenyl)-adamantane-1-carboxylic acid (pyridin-4-ylmethyl)amide], at concentrations of 25 to 50 μM failed to induce formation of the polyubiquitinated forms of Degs1. In contrast to SKi, ABC294640 (25 μM) promotes apoptosis of HEK293T cells via a Degs1-dependent mechanism that is associated with increase...Continue Reading

References

Aug 3, 2001·Apoptosis : an International Journal on Programmed Cell Death·J M WuT C Hsieh
Feb 16, 2002·Methods : a Companion to Methods in Enzymology·K J Livak, T D Schmittgen
Apr 12, 2002·The Journal of Biological Chemistry·Yonghua ZhuDavid A Greenberg
Oct 22, 2002·The Journal of Biological Chemistry·Anat Erdreich-EpsteinMelissa Millard
Mar 5, 2003·Chemical Communications : Chem Comm·Sara J DuncanDudley H Williams
Dec 20, 2003·The Journal of Organic Chemistry·Gemma TriolaAmadeu Llebaria
Mar 5, 2005·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Yi-Ping LiMichael B Reid
Jul 20, 2006·Apoptosis : an International Journal on Programmed Cell Death·N HailR Lotan
Jan 25, 2008·Nature Reviews. Molecular Cell Biology·Yusuf A Hannun, Lina M Obeid
Oct 6, 2009·Experimental Cell Research·Priya SrideviStephen Alexander
Jan 12, 2010·The Journal of Pharmacology and Experimental Therapeutics·Kevin J FrenchCharles D Smith
Apr 21, 2010·The Journal of Biological Chemistry·Giuditta IlluzziAlessandro Prinetti
May 6, 2011·The Journal of Biological Chemistry·Mehrdad RahmaniyanJacqueline M Kraveka
May 7, 2011·Nature Reviews. Immunology·Sarah Spiegel, Sheldon Milstien
Jun 23, 2011·The Journal of Biological Chemistry·Yusuf A Hannun, Lina M Obeid
Jan 3, 2012·Journal of Biochemistry·Hideki Nishitoh
Sep 11, 2012·The International Journal of Biochemistry & Cell Biology·Vincenzo GagliostroPaola Signorelli
May 31, 2014·Journal of Lipid Research·Francesca CingolaniGemma Fabrias
Dec 30, 2014·Current Opinion in Cell Biology·Romain Volmer, David Ron
May 8, 2015·The Journal of Biological Chemistry·Monowarul Mobin SiddiqueScott A Summers
Nov 30, 2016·Biochimica Et Biophysica Acta. General Subjects·Mireia CasasampereGemma Fabrias

❮ Previous
Next ❯

Related Concepts

Related Feeds

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis