A novel chemopreventive mechanism of selenomethionine: Enhancement of APE1 enzyme activity via a Gadd45a, PCNA and APE1 protein complex that regulates p53-mediated base excision repair

Jung,Hwa  Jin; Kim,Hye   Lim; Kim,Yeo  Jin; Weon,Jong-Il; Seo,Young  Rok

doi:10.3892/or.2013.2613

A novel chemopreventive mechanism of selenomethionine: Enhancement of APE1 enzyme activity via a Gadd45a, PCNA and APE1 protein complex that regulates p53-mediated base excision repair

Authors:
- Hwa Jin Jung
- Hye Lim Kim
- Yeo Jin Kim
- Jong-Il Weon
- Young Rok Seo
View Affiliations

Affiliations: Department of Genetics, Albert Einstein College of Medicine, Bronx, NY 10461, USA, Department of Life Science, Institute of Environmental Medicine for Green Chemistry, Dongguk University, Jung-gu, Seoul 100-715, Republic of Korea, Department of Safety Engineering, Dongguk University, Gyeongju, Gyeongbuk 780-714, Republic of Korea
Published online on: July 11, 2013 https://doi.org/10.3892/or.2013.2613
Pages: 1581-1586
Copyright: © Jung et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Organic selenium compounds have been documented to play a role in cancer prevention. Our previous study showed that selenomethionine (SeMet) induces p53 activation without genotoxic effects including apoptosis and cell cycle arrest. In this study, we investigated the mechanism by which organic selenium compounds promote p53-mediated base excision repair (BER) activity. Our data demonstrated for the first time that the interaction between growth arrest and DNA damage-inducible protein 45A (Gadd45a), which is a p53-activated downstream gene, and two BER-mediated repair proteins, proliferating cell nuclear antigen (PCNA) and apurinic/apyrimidinic endonuclease (APE1/Ref-1), was significantly increased in a p53-dependent manner following treatment with organic selenium compounds. Furthermore, we observed that the activity of APE1 was significantly increased in a p53-dependent manner in response to the organic selenium compounds. These results suggest that BER activity is dependent on wild-type p53 activity and is mediated by the modulation of protein interactions between Gadd45a and repair proteins in response to organic selenium compounds. We propose that p53-dependent BER activity is a distinct chemopreventive mechanism mediated by organic selenium compounds, and that this may provide insight into the development of effective chemopreventive strategies against various oxidative stresses that contribute to a variety of human diseases, particularly cancer.

View Figures

View References

1	Ip C: Prophylaxis of mammary neoplasia by selenium supplementation in the initiation and promotion phases of chemical carcinogenesis. Cancer Res. 41:4386–4390. 1981.PubMed/NCBI
2	Ip C, el-Bayoumi K, Upadhyaya P, Ganther H, Vadhanavikit S and Thompson H: Comparative effect of inorganic and organic selenocyanate derivatives in mammary cancer chemoprevention. Carcinogenesis. 15:187–192. 1994. View Article : Google Scholar : PubMed/NCBI
3	Lu J, Jiang C, Kaeck M, Ganther H, Vadhanavikit S, Ip C and Thompson HJ: Cellular and metabolic effects of triphenylselenonium chloride in a mammary cell culture model. Carcinogenesis. 16:513–517. 1995. View Article : Google Scholar : PubMed/NCBI
4	Sinha R, Said TK and Medina D: Organic and inorganic selenium compounds inhibit mouse mammary cell growth in vitro by different cellular pathways. Cancer Lett. 107:277–284. 1996. View Article : Google Scholar : PubMed/NCBI
5	Patterson BH and Levander OA: Naturally occurring selenium compounds in cancer chemoprevention trials: a workshop summary. Cancer Epidemiol Biomarkers Prev. 6:63–69. 1997.PubMed/NCBI
6	Stewart MS, Spallholtz JE, Neldner KH and Pence BC: Selenium compounds have disparate abilities to impose oxidative stress and induce apoptosis. Free Redic Biol Med. 26:42–48. 1999. View Article : Google Scholar : PubMed/NCBI
7	Qiao YL, Dawsey SM, Kamangar F, Fan JH, Abnet CC, Sun XD, Johnson LL, Gail MH, Dong ZW, Yu B, Mark SD and Taylor PR: Total and cancer mortality after supplementation with vitamins and minerals: follow-up of the Linxian General Population Nutrition Intervention Trial. J Natl Cancer Inst. 101:507–518. 2009. View Article : Google Scholar
8	Venkateswaran V, Klotz LH, Ramani M, Sugar LM, Jacob LE, Nam RK and Fleshner NE: A combination of micronutrients is beneficial in reducing the incidence of prostate cancer and increasing survival in the Lady transgenic model. Cancer Prev Res. 2:473–483. 2009. View Article : Google Scholar : PubMed/NCBI
9	Clark LC, Combs GF Jr, Turnbull BW, Slate EH, Chalker DK, Chow J, Davis LS, Glover RA, Graham GF, Gross EG, Krongrad A, Lesher JL Jr, Park HK, Sanders BB Jr, Smith CL and Taylor JR: Effects of selenium supplementation for cancer prevention in patients with carcinoma of the skin. A randomized controlled trial. Nutritional Prevention of Cancer Study Group. JAMA. 276:1957–1963. 1996. View Article : Google Scholar
10	Heinonen OP, Albanes D, Virtamo J, Taylor PR, Huttunen JK, Hartman AM, Haapakoski J, Malila N, Rautalahti M, Ripatti S, Mäenpää H, Teerenhovi L, Koss L, Virolainen M and Edwards BK: Prostate cancer and supplementation with α-tocopherol and β-carotene: incidence and mortality in a controlled trial. J Natl Cancer Inst. 90:440–446. 1998.
11	Seo YR, Kelley MR and Smith ML: Selenomethionine regulation of p53 by a ref1-dependent redox mechanism. Proc Natl Acad Sci USA. 99:14548–14553. 2002. View Article : Google Scholar : PubMed/NCBI
12	Ko LJ and Prives C: p53: puzzle and paradigm. Genes Dev. 10:1054–1072. 1996. View Article : Google Scholar : PubMed/NCBI
13	Giaccia AJ and Kastan MB: The complexity of p53 modulation: emerging patterns from divergent signals. Genes Dev. 12:2973–2983. 1998. View Article : Google Scholar : PubMed/NCBI
14	Prives C and Hall PA: The p53 pathway. J Pathol. 187:112–126. 1999. View Article : Google Scholar
15	Lane DP: Cancer. p53, guardian of the genome. Nature. 358:15–16. 1992. View Article : Google Scholar : PubMed/NCBI
16	Liebermann DA, Hoffman B and Steinman RA: Molecular controls of growth arrest and apoptosis: p53-dependent and independent pathways. Oncogene. 11:199–210. 1995.PubMed/NCBI
17	Hwang BJ, Ford JM, Hanawalt PC and Chu G: Expression of the p48 xeroderma pigmentosum gene is p53-dependent and is involved in global genomic repair. Proc Natl Acad Sci USA. 96:424–428. 1999. View Article : Google Scholar : PubMed/NCBI
18	Jung HJ, Lee JH and Seo YR: Enhancement of methyl methanesulfonate-induced base excision repair in the presence of selenomethionine on p53-dependent pathway. J Med Food. 12:340–344. 2009. View Article : Google Scholar : PubMed/NCBI
19	Smith ML, Ford JM, Hollander MC, Bortnick RA, Amundson SA, Seo YR, Deng CX, Hanawalt PC and Fornace AJ Jr: P53-mediated DNA repair responses to UV-radiation: studies of mouse cells lacking p53, p21, and/or gadd45 genes. Mol Cell Biol. 20:3705–3714. 2000. View Article : Google Scholar : PubMed/NCBI
20	Smith ML, Chen IT, Zhan Q, Bae I, Chen CY, Gilmer TM, Kastan MB, O’Connor PM and Fornace AJ Jr: Interaction of the p53-regulated protein Gadd45 with proliferating cell nuclear antigen. Science. 266:1376–1380. 1994. View Article : Google Scholar : PubMed/NCBI
21	Xia L, Zheng L, Lee HW, Bates SE, Federico L, Shen B and O’Connor TR: Human 3-methyladenine DNA glycosylase: effect of sequence context on excision, association with PCNA, and stimulation by AP endonuclease. J Mol Biol. 346:1259–1274. 2005. View Article : Google Scholar : PubMed/NCBI
22	Jung HJ, Kim EH, Mun JY, Park S, Smith ML, Han SS and Seo YR: Base excision DNA repair defect in Gadd45a-deficient cells. Oncogene. 26:7517–7525. 2007. View Article : Google Scholar : PubMed/NCBI
23	Kastan MB, Zhan Q, el-Deiry WS, Carrier F, Jacks T, Walsh WV, Plunkett BS, Vogelstein B and Fornace AJ Jr: A mammalian cell cycle checkpoint pathway utilizing p53 and GADD45 is defective in ataxia-telangiectasia. Cell. 71:587–597. 1992. View Article : Google Scholar : PubMed/NCBI
24	Smith ML, Chen IT, Zhan Q, O’Connor PM and Fornace AJ Jr: Involvement of the p53 tumor suppressor in repair of u.v.-type DNA damage. Oncogene. 10:1053–1059. 1995.PubMed/NCBI
25	Seeberg E, Eide L and Bjørås M: The base excision repair pathway. Trans Biochem Sci. 20:391–397. 1995. View Article : Google Scholar
26	Sung JS and Demple B: Roles of base excision repair subpathways in correcting oxidized abasic sites in DNA. FEBS J. 273:1620–1629. 2006. View Article : Google Scholar : PubMed/NCBI
27	Lindahl T and Andersson A: Rate of chain breakage at apurinic sites in double-stranded deoxyribonucleic acid. Biochemistry. 11:3618–3623. 1972. View Article : Google Scholar : PubMed/NCBI
28	Lindahl T and Nyberg B: Rate of depurination of native deoxyribonucleic acid. Biochemistry. 11:3610–3618. 1972. View Article : Google Scholar : PubMed/NCBI
29	Lippman SM, Klein EA, Goodman PJ, Lucia MS, Thompson IM, Ford LG, Parnes HL, Minasian LM, Gaziano JM, Hartline JA, Parsons JK, Bearden JD III, Crawford ED, Goodman GE, Claudio J, Winquist E, Cook ED, Karp DD, Walther P, Lieber MM, Kristal AR, Darke AK, Arnold KB, Ganz PA, Santella RM, Albanes D, Taylor PR, Probstfield JL, Jagpal TJ, Crowley JJ, Meyskens FL Jr, Baker LH and Coltman CA Jr: Effect of selenium and vitamin E on risk of prostate cancer and other cancers: the Selenium and Vitamin E Cancer Prevention Trial (SELECT). JAMA. 301:39–51. 2009. View Article : Google Scholar : PubMed/NCBI
30	Gaiddon C, Moorthy NC and Prives C: Ref-1 regulates the transactivation and pro-apoptotic functions of p53 in vivo. EMBO J. 18:5609–5621. 1999. View Article : Google Scholar
31	Offer H, Zurer I, Banfalvi G, Reha’k M, Falcovitz A, Milyavsky M, Goldfinger N and Rotter V: p53 modulates base excision repair activity in a cell cycle-specific manner after genotoxic stress. Cancer Res. 61:88–96. 2001.PubMed/NCBI
32	Zhou J, Ahn J, Wilson SH and Prives C: A role for p53 in base excision repair. EMBO J. 20:914–923. 2001. View Article : Google Scholar : PubMed/NCBI
33	Lee YS and Chung MH: Base excision repair synthesis of DNA containing 8-oxoguanine in Escherichia coli. Exp Mol Med. 35:106–112. 2003. View Article : Google Scholar : PubMed/NCBI
34	Adimoolam S and Ford JM: p53 and DNA damage-inducible expression of the xeroderma pigmentosum group C gene. Proc Natl Acad Sci USA. 99:12985–12990. 2002. View Article : Google Scholar : PubMed/NCBI
35	Vairapandi M, Azam N, Balliet AG, Hoffman B and Liebermann DA: Characterization of MyD118, Gadd45, and proliferating cell nuclear antigen (PCNA) interacting domains. PCNA impedes MyD118 and Gadd45-mediated negative growth control. J Biol Chem. 275:16810–16819. 2000. View Article : Google Scholar : PubMed/NCBI
36	Seo YR, Sweeney C and Smith ML: Selenomethionine induction of DNA repair response in human fibroblasts. Oncogene. 21:3663–3669. 2002. View Article : Google Scholar : PubMed/NCBI
37	Hanson S, Kim E and Deppert W: Redox factor 1 (Ref-1) enhances specific DNA binding of p53 by promoting p53 tetramerization. Oncogene. 24:1641–1647. 2005. View Article : Google Scholar : PubMed/NCBI