title: Downregulation of the polyamine regulator spermidine/spermine N(1)-acetyltransferase by Epstein-Barr virus in a Burkitt's lymphoma cell line.
abstract: Transition of Akata Burkitt's lymphoma (BL) from a malignant to nonmalignant phenotype upon loss of Epstein-Barr virus (EBV) is evidence for a viral contribution to tumorigenesis despite the tight restriction of EBV gene expression in BL. Examination of global cellular gene expression in Akata subclones that retained or lost EBV identified spermidine/spermine N(1)-acetyltransferase (SAT1), an inducible enzyme whose catabolism of polyamines affects both apoptosis and cell growth, as one of a limited number of cellular genes downregulated by EBV. Re-infection of the EBV-negative Akata clone reduced SAT1 mRNA to a level comparable with the parental EBV-positive Akata. EBV-positive Akata cells demonstrated decreased SAT1 enzyme activity concomitant with altered intracellular polyamine constituents. Reduction of SAT1 in EBV-positive BL was a transcriptional effect. Forced expression of the viral BCL2 homologue, BHRF1, in an EBV-negative Akata clone reduced SAT1 mRNA. Thus, EBV repression of polyamine catabolism becomes a complementary alteration to dysregulated c-myc enhancement of polyamine synthesis in BL and favorable to BL lymphomagenesis.
authors.affiliation: Center for Tumor and Molecular Virology and Department of Microbiology and Immunology, Louisiana State University Health Sciences Center, Shreveport, LA 71130, USA.
authors.forename: Mingxia
authors.initials: M
authors.lastname: Shi
authors.forename: Yan-Jun
authors.initials: YJ
authors.lastname: Gan
authors.forename: Timothy O
authors.initials: TO
authors.lastname: Davis
authors.forename: Rona S
authors.initials: RS
authors.lastname: Scott
mesh_terms: D000123:Acetyltransferases / Q000235:genetics* / Q000378:metabolism; D002051:Burkitt Lymphoma / Q000201:enzymology* / Q000235:genetics / Q000821:virology; D045744:Cell Line, Tumor; D015536:Down-Regulation; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D011073:Polyamines / Q000378:metabolism*; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism; D000099228:Diamine N-Acetyltransferase
chemical_list: D000123:Acetyltransferases; D011073:Polyamines; D014764:Viral Proteins; D000099228:Diamine N-Acetyltransferase; C083278:BHRF1 protein, Human herpesvirus 4
keywords: Akata; Burkitt's lymphoma; EBV; Polyamines; Spermidine/spermine N(1)-acetyltransferase; c-myc
references.citation: J Biol Chem. 1993 Sep 5;268(25):19118-25
references.pmid: 8360194
references.citation: Eur J Biochem. 2004 Mar;271(5):877-94
references.pmid: 15009201
references.citation: J Virol. 1998 Sep;72(9):7577-82
references.pmid: 9696856
references.citation: Mol Cell Biol. 1999 Mar;19(3):1651-60
references.pmid: 10022853
references.citation: Blood. 2005 Mar 1;105(5):2135-7
references.pmid: 15522957
references.citation: Proc Natl Acad Sci U S A. 1982 Dec;79(24):7837-41
references.pmid: 6818551
references.citation: J Virol. 1998 Nov;72(11):9150-6
references.pmid: 9765461
references.citation: Mol Cell Biol. 2001 Feb;21(3):691-702
references.pmid: 11154257
references.citation: Proc Natl Acad Sci U S A. 1997 Oct 14;94(21):11557-62
references.pmid: 9326648
references.citation: Nature. 1982 Jun 24;297(5868):690-1
references.pmid: 6283366
references.citation: EMBO J. 1987 Sep;6(9):2743-51
references.pmid: 2824192
references.citation: Proc Natl Acad Sci U S A. 1971 Nov;68(11):2818-21
references.pmid: 5288261
references.citation: Biochem J. 1996 Jan 15;313 ( Pt 2):691-6
references.pmid: 8573111
references.citation: EMBO J. 2000 Dec 15;19(24):6742-50
references.pmid: 11118209
references.citation: Proc Natl Acad Sci U S A. 1998 Sep 15;95(19):11140-5
references.pmid: 9736703
references.citation: Nat Rev Cancer. 2004 Oct;4(10):781-92
references.pmid: 15510159
references.citation: Cell Biol Int. 2008 Jan;32(1):66-74
references.pmid: 17920946
references.citation: FASEB J. 1993 May;7(8):653-61
references.pmid: 8500690
references.citation: Biochim Biophys Acta. 1981 Jul 17;675(3-4):373-8
references.pmid: 6168299
references.citation: J Virol. 1975 Nov;16(5):1254-64
references.pmid: 1185852
references.citation: J Virol. 2000 Nov;74(21):10223-8
references.pmid: 11024153
references.citation: Proc Natl Acad Sci U S A. 1982 Dec;79(24):7824-7
references.pmid: 6961453
references.citation: FEBS Lett. 1980 Dec 1;121(2):292-4
references.pmid: 6257550
references.citation: Proc Natl Acad Sci U S A. 1993 Aug 15;90(16):7804-8
references.pmid: 8356088
references.citation: J Infect Dis. 2004 Sep 1;190(5):979-84
references.pmid: 15295705
references.citation: J Virol. 2006 Mar;80(5):2548-65
references.pmid: 16474161
references.citation: J Virol. 1987 Sep;61(9):2902-9
references.pmid: 3039177
references.citation: Microbios. 1973;7(25):61-8
references.pmid: 4697931
references.citation: J Chromatogr. 1986 Jul 11;380(1):19-32
references.pmid: 3745383
references.citation: Proc Natl Acad Sci U S A. 2003 Nov 25;100(24):14269-74
references.pmid: 14603034
references.citation: J Virol. 1994 Sep;68(9):6069-73
references.pmid: 8057484
references.citation: Nucleic Acids Res. 1986 Sep 11;14(17):7103-14
references.pmid: 3020506
references.citation: Blood. 1995 Sep 1;86(5):1893-902
references.pmid: 7655018
references.citation: J Virol. 2001 Feb;75(3):1561-4
references.pmid: 11152530
references.citation: Virology. 2009 Apr 10;386(2):387-97
references.pmid: 19217135
references.citation: Virus Genes. 1991 Apr;5(2):147-56
references.pmid: 1647567
references.citation: Proc Natl Acad Sci U S A. 2006 Oct 3;103(40):14935-40
references.pmid: 17001014
references.citation: J Virol. 1992 Dec;66(12):7461-8
references.pmid: 1331531
references.citation: Biochem Soc Trans. 1985 Apr;13(2):331-2
references.pmid: 2991036
references.citation: RNA. 2006 Aug;12(8):1569-82
references.pmid: 16809818
references.citation: Biochemistry. 1996 Nov 12;35(45):14436-44
references.pmid: 8916930
references.citation: Virology. 2002 Jun 5;297(2):163-71
references.pmid: 12083816
references.citation: Mol Pharmacol. 2003 Nov;64(5):1153-9
references.pmid: 14573765
references.citation: J Virol. 2005 May;79(9):5499-506
references.pmid: 15827164
references.citation: EMBO J. 2002 Mar 1;21(5):954-65
references.pmid: 11867523
references.citation: Exp Cell Res. 2001 Jun 10;266(2):333-41
references.pmid: 11399061
references.citation: Proc Natl Acad Sci U S A. 1993 Sep 15;90(18):8479-83
references.pmid: 8397406
references.citation: J Infect Dis. 1998 May;177(5):1194-201
references.pmid: 9593003
references.citation: J Exp Med. 2000 Oct 16;192(8):1183-90
references.pmid: 11034608
references.citation: Biochem J. 1995 Jan 15;305 ( Pt 2):451-8
references.pmid: 7832759
references.citation: J Gen Virol. 1974 Mar;22(3):451-4
references.pmid: 4818280
references.citation: Exp Cell Res. 2001 Apr 15;265(1):174-83
references.pmid: 11281655
references.citation: J Gen Virol. 1999 Aug;80 ( Pt 8):2193-2203
references.pmid: 10466819
references.citation: Cancer Res. 1992 May 1;52(9):2424-30
references.pmid: 1568212
references.citation: Biochem Pharmacol. 1989 May 1;38(9):1435-42
references.pmid: 2497746
references.citation: Proc Natl Acad Sci U S A. 1988 Jun;85(11):3678-82
references.pmid: 2836854
references.citation: J Virol. 1999 Dec;73(12):9827-31
references.pmid: 10559294
references.citation: Essays Biochem. 2009 Nov 04;46:11-24
references.pmid: 20095967
references.citation: Clin Cancer Res. 1999 May;5(5):945-51
references.pmid: 10353725
references.citation: J Mol Biol. 1975 Nov 5;98(3):503-17
references.pmid: 1195397
references.citation: J Immunol. 2003 Sep 1;171(5):2446-52
references.pmid: 12928392
references.citation: PLoS Pathog. 2009 Mar;5(3):e1000341
references.pmid: 19283066