title: B-cell translocation gene 2 mediates crosstalk between PI3K/Akt1 and NFκB pathways which enhances transcription of MnSOD by accelerating IκBα degradation in normal and cancer cells.
abstract: BACKGROUND
  B-cell translocation gene 2 (BTG2) belongs to antiproliferative (ARPO) gene family and the expression of BTG2, human ortholog of rat PC3 and mouse TIS21 gene, has been shown to render cancer cells more sensitive to doxorubicin treatment by upregulating MnSOD expression without regulating any other reactive oxygen species (ROS) scavenging enzymes.
  
  
  RESULTS
  In the present study, by employing exogenous and endogenous BTG2/TIS21/Pc3 expression by transfection and transduction analyses, and by knockdown of gene expression using RNA interference or using gene knockout cells, we observed that BTG2 increased the binding of activated NF-κB (p65/RelA) to the enhancer element of MnSOD gene in the 2nd intron, which was regulated by p-Akt1, and the induction of MnSOD by BTG2 was accompanied with subsequent downregulation of ROS level and cyclin B1 biosynthesis along with the increase of p21WAF1, resulting in the G2/M arrest independent of p53.
  
  
  CONCLUSIONS
  These results show for the first time that BTG2 mediates crosstalk between PI3K-Akt1 and NF-κB pathways, which regulates p53-independent induction of G2/M phase arrest both in normal and cancer cells.
authors.affiliation: Department of Biochemistry and Molecular Biology, BK21 Cell Transformation and Restoration, Ajou University School of Medicine, Suwon 443-721, Republic of Korea. iklim@ajou.ac.kr.
authors.forename: Santhoshkumar
authors.initials: S
authors.lastname: Sundaramoorthy
authors.forename: Min Sook
authors.initials: MS
authors.lastname: Ryu
authors.forename: In Kyoung
authors.initials: IK
authors.lastname: Lim
mesh_terms: D006367:HeLa Cells; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D020672:I-kappa B Proteins / Q000378:metabolism; D017874:Immediate-Early Proteins / Q000235:genetics / Q000378:metabolism*; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism*; D009369:Neoplasms / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D020672:I-kappa B Proteins; D017874:Immediate-Early Proteins; D016328:NF-kappa B; C000606204:NFKBIA protein, human; C000606205:Nfkbia protein, mouse; C000606206:Nfkbia protein, rat; D025521:Tumor Suppressor Proteins; D000072000:NF-KappaB Inhibitor alpha; C070114:BTG2 protein, human; D006861:Hydrogen Peroxide; D013482:Superoxide Dismutase; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt
references.citation: Aging (Albany NY). 2011 Feb;3(2):102-7
references.pmid: 21386137
references.citation: J Endocrinol. 2010 Mar;204(3):311-8
references.pmid: 20007738
references.citation: Cancer Res. 2013 Jan 1;73(1):428-38
references.pmid: 23047866
references.citation: J Biol Chem. 2005 Jun 3;280(22):21256-63
references.pmid: 15788397
references.citation: Free Radic Biol Med. 2012 Jun 1-15;52(11-12):2209-22
references.pmid: 22561706
references.citation: Neuroreport. 2002 Mar 25;13(4):417-22
references.pmid: 11930152
references.citation: Int J Cancer. 1992 May 28;51(3):476-80
references.pmid: 1592538
references.citation: J Cancer Res Clin Oncol. 1995;121(5):279-84
references.pmid: 7768965
references.citation: Free Radic Res Commun. 1993;19(3):203-13
references.pmid: 8244089
references.citation: Mol Cancer Res. 2005 Jun;3(6):345-53
references.pmid: 15972853
references.citation: Mol Cell Biol. 2000 Mar;20(5):1797-815
references.pmid: 10669755
references.citation: J Biol Chem. 2008 Nov 28;283(48):33110-8
references.pmid: 18840609
references.citation: Antioxid Redox Signal. 2004 Jun;6(3):537-48
references.pmid: 15130280
references.citation: DNA Cell Biol. 1999 Sep;18(9):709-22
references.pmid: 10492402
references.citation: Oncogene. 2004 Oct 28;23(50):8310-9
references.pmid: 15378000
references.citation: Clin Exp Metastasis. 2012 Dec;29(8):901-13
references.pmid: 22562501
references.citation: Genes Dev. 2006 Jan 15;20(2):236-52
references.pmid: 16418486
references.citation: Cancer Res. 2010 Mar 15;70(6):2274-84
references.pmid: 20197462
references.citation: J Biol Chem. 2011 Oct 14;286(41):36076-36085
references.pmid: 21862580
references.citation: Mol Cell Biol. 1996 Apr;16(4):1295-304
references.pmid: 8657102
references.citation: J Biol Chem. 2012 Sep 7;287(37):31503-14
references.pmid: 22493435
references.citation: Int J Mol Sci. 2011;12(10):7114-62
references.pmid: 22072939
references.citation: Nat Genet. 1996 Dec;14(4):482-6
references.pmid: 8944033
references.citation: J Biol Chem. 1991 Aug 5;266(22):14511-8
references.pmid: 1713584
references.citation: EMBO J. 2008 Apr 9;27(7):1039-48
references.pmid: 18337750
references.citation: J Cell Sci. 2012 Jul 1;125(Pt 13):3144-52
references.pmid: 22427690
references.citation: Nature. 2002 Sep 19;419(6904):316-21
references.pmid: 12239572
references.citation: Oncogene. 2001 Apr 26;20(18):2225-34
references.pmid: 11402317
references.citation: Oncogene. 2011 Jul 7;30(27):3084-95
references.pmid: 21339742
references.citation: PLoS One. 2012;7(6):e39945
references.pmid: 22768179
references.citation: Trends Biochem Sci. 2009 Dec;34(12):640-7
references.pmid: 19828319
references.citation: Exp Cell Res. 2004 Sep 10;299(1):159-70
references.pmid: 15302583
references.citation: Biochem Biophys Res Commun. 2013 May 10;434(3):559-65
references.pmid: 23583382
references.citation: Carcinogenesis. 2001 Aug;22(8):1271-9
references.pmid: 11470758
references.citation: Cancer Res. 2004 Mar 1;64(5):1632-8
references.pmid: 14996721
references.citation: J Pharmacol Exp Ther. 2000 Dec;295(3):870-8
references.pmid: 11082419
references.citation: Biochem J. 2001 Jan 1;353(Pt 1):147-156
references.pmid: 11115408
references.citation: J Neurosci. 2012 Oct 31;32(44):15547-64
references.pmid: 23115191
references.citation: Proc Natl Acad Sci U S A. 1991 Apr 15;88(8):3353-7
references.pmid: 1849653
references.citation: Biochim Biophys Acta. 2008 May;1783(5):935-40
references.pmid: 18269916
references.citation: FEBS Lett. 2001 May 25;497(2-3):67-72
references.pmid: 11377414
references.citation: J Cell Physiol. 2010 Jan;222(1):66-72
references.pmid: 19746446
references.citation: Tissue Cell. 2002 Feb;34(1):28-32
references.pmid: 11989967
references.citation: Hepatology. 2008 May;47(5):1533-43
references.pmid: 18393292
references.citation: Proc Natl Acad Sci U S A. 1993 Apr 1;90(7):3113-7
references.pmid: 8464931
references.citation: Proc Natl Acad Sci U S A. 1995 Nov 7;92(23):10599-603
references.pmid: 7479848
references.citation: Mol Carcinog. 1998 Sep;23(1):25-35
references.pmid: 9766435
references.citation: Photochem Photobiol. 2012 Sep-Oct;88(5):1149-56
references.pmid: 22540890
references.citation: Nat Rev Cancer. 2012 Oct;12(10):685-98
references.pmid: 23001348
references.citation: Biochem J. 2002 Mar 1;362(Pt 2):401-12
references.pmid: 11853549
references.citation: Stem Cells. 2008 Sep;26(9):2339-48
references.pmid: 18556508
references.citation: Science. 1956 Feb 24;123(3191):309-14
references.pmid: 13298683