title: Study of global transcriptional changes of N-GlcNAc2 proteins-producing T24 bladder carcinoma cells under glucose deprivation.
abstract: Increased levels of N-linked (β-N- acetylglucosamine)2 [N-GlcNAc2]-modified proteins have been recognized to be an effective response to glucose deprivation. In the first step of this study, using a next generation sequencer, we investigated the global transcriptional changes induced by glucose deprivation in a T24 bladder carcinoma cell line, producing N-GlcNAc2-modified proteins under glucose deprivation. Our transcriptome analysis revealed significant up-regulation of the UDP-GlcNAc biosynthesis pathway and unfolded protein response genes, and down-regulation of G2/M transition-related genes containing mitotic kinases. Our biological analysis confirmed that N-GlcNAc2-modified proteins were localized with BiP proteins in the ER. G2/M arrest was caused by glucose deprivation in T24 cells. Moreover, the knockdown of unfolded protein response genes induced the expressional recovery of mitotic kinases under glucose deprivation. Taken together, our results suggest N-GlcNAc2-modified proteins produced under glucose deprivation caused unfolded protein response in the ER, and that this response induced G2/M arrest.
authors.affiliation: Central Reseach Laboratory, Shiga University of Medical Science, Otsu, Shiga, Japan. isono@belle.shiga-med.ac.jp
authors.forename: Takahiro
authors.initials: T
authors.lastname: Isono
authors.forename: Tokuhiro
authors.initials: T
authors.lastname: Chano
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Okabe
authors.forename: Masafumi
authors.initials: M
authors.lastname: Suzaki
mesh_terms: D000117:Acetylglucosamine / Q000378:metabolism*; D002277:Carcinoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D004721:Endoplasmic Reticulum / Q000235:genetics / Q000378:metabolism; D000091342:Endoplasmic Reticulum Chaperone BiP; D059565:G2 Phase Cell Cycle Checkpoints / Q000235:genetics; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D005947:Glucose / Q000172:deficiency*; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D056811:Unfolded Protein Response / Q000235:genetics; D001743:Urinary Bladder / Q000378:metabolism* / Q000473:pathology; D001749:Urinary Bladder Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
chemical_list: D000091342:Endoplasmic Reticulum Chaperone BiP; D006360:Heat-Shock Proteins; D009363:Neoplasm Proteins; D011494:Protein Kinases; D005947:Glucose; D000117:Acetylglucosamine
references.citation: Oncogene. 2011 Jan 20;30(3):253-64
references.pmid: 20972457
references.citation: Science. 2008 Aug 15;321(5891):956-60
references.pmid: 18599741
references.citation: Cancer Res. 2005 Jun 15;65(12):5181-9
references.pmid: 15958562
references.citation: J Biol Chem. 2008 Mar 7;283(10):6050-7
references.pmid: 18174169
references.citation: J Cell Sci. 2007 Aug 1;120(Pt 15):2479-87
references.pmid: 17646672
references.citation: Yeast. 1998 Jun 15;14(8):773-81
references.pmid: 9675821
references.citation: Biochim Biophys Acta. 2010 Feb;1800(2):96-106
references.pmid: 19647786
references.citation: Curr Pharm Des. 2010 Jan;16(1):69-78
references.pmid: 20214619
references.citation: Science. 2011 Nov 25;334(6059):1081-6
references.pmid: 22116877
references.citation: Nat Methods. 2008 Jul;5(7):621-8
references.pmid: 18516045
references.citation: J Biol Chem. 2008 May 9;283(19):13009-20
references.pmid: 18353774
references.citation: Breast Cancer Res Treat. 2000 Jan;59(1):15-26
references.pmid: 10752676
references.citation: FEBS Lett. 2009 Jan 5;583(1):163-7
references.pmid: 19059404
references.citation: Endocr Rev. 2004 Oct;25(5):807-30
references.pmid: 15466941
references.citation: Nat Rev Mol Cell Biol. 2001 Jan;2(1):21-32
references.pmid: 11413462
references.citation: Anal Biochem. 1987 Apr;162(1):156-9
references.pmid: 2440339
references.citation: Biochim Biophys Acta. 2007 Jan;1775(1):92-102
references.pmid: 17014965
references.citation: Cancer Metastasis Rev. 2009 Jun;28(1-2):219-23
references.pmid: 19172382
references.citation: Cell Mol Life Sci. 2006 Apr;63(7-8):781-95
references.pmid: 16465440
references.citation: J Biol Chem. 2011 Nov 11;286(45):39431-8
references.pmid: 21949237
references.citation: Cancer Res. 2007 Apr 15;67(8):3496-9
references.pmid: 17440054
references.citation: Am J Physiol Cell Physiol. 2005 Jan;288(1):C148-55
references.pmid: 15342340
references.citation: J Biol Chem. 2009 Dec 11;284(50):34777-84
references.pmid: 19833729
references.citation: J Biol Chem. 2002 Sep 20;277(38):35386-92
references.pmid: 12095988
references.citation: Trends Endocrinol Metab. 2009 Nov;20(9):436-43
references.pmid: 19800252
references.citation: Genes Dev. 2010 Dec 15;24(24):2784-99
references.pmid: 21106670
references.citation: Hum Pathol. 2008 Jul;39(7):1042-9
references.pmid: 18482745
references.citation: Physiol Rev. 2008 Jan;88(1):249-86
references.pmid: 18195088
references.citation: J Mol Med (Berl). 2009 Nov;87(11):1053-60
references.pmid: 19705082
references.citation: Nature. 2007 Apr 26;446(7139):1017-22
references.pmid: 17460662
references.citation: J Biol Chem. 2009 Feb 6;284(6):3425-32
references.pmid: 19073609
references.citation: Int J Cancer. 1973 May;11(3):765-73
references.pmid: 4133950
references.citation: PLoS One. 2011 Apr 19;6(4):e18959
references.pmid: 21526146
references.citation: Biochim Biophys Acta. 2004 Jul 6;1673(1-2):13-28
references.pmid: 15238246