TIS21/BTG2/PC3 upregulates MnSOD expression via activation of NF-κB pathway in HeLa cells
Sundaramoorthy, Santhoshkumar; Ryu, Min Sook; Lim, In Kyoung
Department of Biochemistry & Molecular Biology
TIS21 (TPA inducible sequences 21)/BTG2/PC3 has been known as one of the early growth response genes and isolated from 3T3 fibroblasts treated with TPA. Together with BTG1, BTG3/ANA/Rbtg3, BTG4 and Tob genes, it belongs to the family of antiproliferative (APRO) genes. BTG2 acts as LXXLL-dependent co-repressor of androgen receptor transcriptional activity. We have previously reported that over expression of TIS21 itself increases endogenous expression of MnSOD, and it is enhanced by doxorubicin co treatment along with H2O2 burst in HeLa cells. Moreover, we for the first time identified TIS21 gene as a potential tumor suppressor in thymic carcinoma. In the present study, a mechanism of MnSOD induction by TIS21 was investigated; Over expression of TIS21/BTG2/PC3 increased degradation of IKB–α and the interaction of NF-kB with its responsive element located in the intron-2 enhancer region of MnSOD gene. The findings could be confirmed by immunoblot and ChIP analyses, respectively. Our data clearly indicate that TIS21/BTG2/PC3 could up regulate the expression of MnSOD via activation of NF-kB pathway. We are going to discuss about the upstream signals activating NF-kB pathway in response to forced expression of TIS21/BTG2/PC3 in HeLa cells and finally elucidate phenotypes of NFkB activation.
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