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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.

Authors
Sundaramoorthy, S; Ryu, MS; Lim, IK
Citation
Cell communication and signaling : CCS, 11:69-69, 2013
Journal Title
Cell communication and signaling : CCS
ISSN
1478-811X
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.
MeSH terms
HeLa CellsHumansHydrogen Peroxide/metabolismI-kappa B Proteins/metabolismImmediate-Early Proteins/genetics/*metabolismNF-kappa B/*metabolismNeoplasms/metabolismPhosphatidylinositol 3-Kinases/*metabolismProto-Oncogene Proteins c-akt/*metabolismSuperoxide Dismutase/genetics/*metabolismTumor Suppressor Proteins/genetics/*metabolism
DOI
10.1186/1478-811X-11-69
PMID
24047462
Appears in Collections:
Journal Papers > Research Organization > BK21
Journal Papers > School of Medicine / Graduate School of Medicine > Biochemistry & Molecular Biology
AJOU Authors
유, 민숙임, 인경
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