Methylglyoxal downregulates Raf-1 protein through a ubiquitination-mediated mechanism

The International Journal of Biochemistry & Cell Biology
Jun DuShaohui Cai

Abstract

Abnormal accumulation of methylglyoxal, a physiological glucose metabolite, is considered a potential link between hyperglycemia and diabetes complications. Evidence has shown that methylglyoxal modifies cellular proteins by glycation and oxidation, resulting in dysfunction or loss of cellular proteins. Raf-1 protein-serine/threonine kinase serves as a central switch board in the transmission of many growth and developmental signals. It was reported that Raf-1 levels appear to decrease in some diabetic subjects. But the potential mechanisms have not yet been clarified. Here, we tested the hypothesis that methylglyoxal-mediated proteolysis might contribute to the downregulation of Raf-1 levels. We observed that a rapid and detectable decrease in Raf-1 protein levels was induced by methylglyoxal, which was accelerated by treating with a Raf-1 activator, phorbol-12-myristate-13-acetate, and by expressing active forms of Raf-1 and Ras. Moreover, immunoprecipitation and immunoblotting assays showed that co-treatment of cells with methylglyoxal and phorbol-12-myristate-13-acetate caused dramatic ubiquitination in both total intracellular proteins and Raf-1. Blocking phosphorylation with the protein kinase C inhibitor bisindolylmaleim...Continue Reading

References

Jan 1, 1993·Molecular Aspects of Medicine·P J Thornalley
Dec 10, 1996·Proceedings of the National Academy of Sciences of the United States of America·C SchneiderF U Hartl
Apr 1, 1998·Proceedings of the Society for Experimental Biology and Medicine·W B Pratt
Apr 26, 2002·Neuroreport·Gerald MünchGlenda M Halliday
Apr 30, 2002·Diabetes·Manuel Portero-OtínAnne Nègre-Salvayre
Jun 21, 2002·Biochemical and Biophysical Research Communications·Stéphane ManentiJean-Marie Darbon
Mar 29, 2003·Diabetes·D Steven ZatechkaMarjorie F Lou
Sep 24, 2004·Experimental Eye Research·M Satish KumarG Bhanuprakash Reddy
Oct 14, 2004·Amyloid : the International Journal of Experimental and Clinical Investigation : the Official Journal of the International Society of Amyloidosis·Jaime E RofinaErik Gruys

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Citations

Jun 6, 2009·Antioxidants & Redox Signaling·Anne Negre-SalvayreManuel Portero-Otín
Jun 7, 2008·Drug Metabolism and Drug Interactions·David L Vander Jagt
Aug 10, 2010·The International Journal of Biochemistry & Cell Biology·Guan-Min JiangJun Du
Aug 28, 2009·Trends in Endocrinology and Metabolism : TEM·Claire L Price, Stella C Knight
Jan 1, 2015·Nature Plants·Subramanian SankaranarayananMarcus A Samuel
May 2, 2008·Annals of the New York Academy of Sciences·Timo M BuetlerThierry Delatour
May 2, 2008·Annals of the New York Academy of Sciences·Naila Rabbani, Paul J Thornalley
Aug 8, 2015·Chemical Research in Toxicology·Sireesh DornadulaRamkumar Kunka Mohanram
Oct 22, 2014·The FEBS Journal·Su AnTian-Rui Xu
Feb 12, 2011·Seminars in Cell & Developmental Biology·Yoshiharu InoueWataru Nomura
Mar 18, 2017·International Journal of Molecular Sciences·Thomas SchmochThorsten Brenner
Jul 16, 2014·Molecular and Cellular Biology·Eun Ryoung JangEmilia Galperin
Sep 13, 2011·Amino Acids·Ross Milne, Seymour Brownstein
Mar 3, 2012·G3 : Genes - Genomes - Genetics·Shawn HoonCorey Nislow
Feb 24, 2019·International Journal of Molecular Sciences·Christina J McTavishCaroline Schild-Poulter
Apr 8, 2010·Archives of Biochemistry and Biophysics·Ann E PattinNorbert W Seidler

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