Abstract
Human NAD(P)H: quinone oxidoreductase 1 (NQO1) catalyzes the obligatory two-electron reduction of quinones. For this peculiar catalytic mechanism, the enzyme is considered an important cytoprotector. The NQO1 gene is expressed in all human tissues, unless a polymorphism due to C609T point mutation is present. This polymorphism produces a null phenotype in the homozygous condition and reduced enzyme activity in the heterozygous one. We previously demonstrated that two cell lines of haematopoietic origin, HL60 and Raji cells, possess the same heterozygous genotype, but different phenotypes; as expected for a heterozygous condition the HL60 cell line showed a low level of enzyme activity, while the Raji cell line appeared as null phenotype. The level of NQO1 mRNA was similar in the two cell lines and the different phenotype was not due to additional mutations or to expression of alternative splicing products. Here we show that in Raji BL cell line with heterozygous genotype the null NQO1 phenotype is due to 20S proteasome degradation of wild type and mutant protein isoforms and is not directly linked to C609T polymorphism. This finding may have important implications in B-cell differentiation, in leukaemia risk evaluation and in c...Continue Reading
References
May 7, 1976·Analytical Biochemistry·M M Bradford
Jun 1, 1982·Archives of Biochemistry and Biophysics·C LindL Ernster
Jun 1, 1993·Cancer Metastasis Reviews·D RossN W Gibson
Mar 6, 1996·Journal of the National Cancer Institute·S A FitzsimmonsA D Lewis
Mar 19, 1996·Proceedings of the National Academy of Sciences of the United States of America·R E BeyerG Lenaz
May 2, 1997·The Journal of Biological Chemistry·A M EleuteriM Orlowski
Apr 21, 1997·The Journal of Experimental Medicine·M LeistP Nicotera
Feb 25, 2000·Protein Expression and Purification·A M EleuteriE Fioretti
Nov 10, 2001·Toxicology Letters·D SiegelD Ross
Mar 17, 2004·Oncogene·Maria G Masucci
Jul 13, 2004·Cancer Treatment Reviews·S DansonM Ranson
Mar 8, 2005·Molecular Cell·Gad AsherChaim Kahana
Aug 15, 2006·The Journal of Biological Chemistry·Karim IskanderAnil K Jaiswal
Jan 12, 2008·Cell Death and Differentiation·D MasedaR E Voll
Jun 19, 2008·Biochimica Et Biophysica Acta·Isabelle Jariel-EncontreMarc Piechaczyk
Oct 24, 2008·American Journal of Epidemiology·Neela GuhaPatricia A Buffler
Jan 24, 2009·Journal of Molecular Biology·James M BaughEvgeny V Pilipenko
Apr 18, 2009·Molecular Aspects of Medicine·Tobias JungTilman Grune
Jul 18, 2009·Science·Chunaram ChoudharyMatthias Mann
Dec 1, 2009·Biochemical and Biophysical Research Communications·Qing GengMatthias Majetschak
Feb 6, 2010·Cancer Letters·William Ka Kei WuJoseph Jao Yiu Sung
Apr 7, 2010·Archives of Biochemistry and Biophysics·Albena T Dinkova-Kostova, Paul Talalay
Aug 26, 2010·Science Signaling·Albrecht MoritzMichael J Comb
Sep 2, 2010·Cell Research·Hongbiao HuangJinbao Liu