Effects of the MDM2 Promoter SNP285 and SNP309 on Sp1 Transcription Factor Binding and Cancer Risk

Overview

Journal Transcription

Specialty Molecular Biology

Date 2012 Jan 11

PMID 22231115

Citations 23

Authors

Stian Knappskog

Per E Lonning

Affiliations

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Abstract

The proto-oncogene MDM2 inhibits p53 and plays a key role in cell growth control and apoptosis. Identification of two antagonizing MDM2 polymorphisms, SNP285 and SNP309, affecting cancer risk through modulation of Sp1 transcription factor binding, shed new light on the biological activity and phylogeny of this gene.

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References

Post S, Quintas-Cardama A, Pant V, Iwakuma T, Hamir A, Jackson J . A high-frequency regulatory polymorphism in the p53 pathway accelerates tumor development. Cancer Cell. 2010; 18(3):220-30. PMC: 2944041. DOI: 10.1016/j.ccr.2010.07.010. View

Landers J, Cassel S, GEORGE D . Translational enhancement of mdm2 oncogene expression in human tumor cells containing a stabilized wild-type p53 protein. Cancer Res. 1997; 57(16):3562-8. View

Montes de Oca Luna R, Wagner D, Lozano G . Rescue of early embryonic lethality in mdm2-deficient mice by deletion of p53. Nature. 1995; 378(6553):203-6. DOI: 10.1038/378203a0. View

Martin K, Trouche D, Hagemeier C, Sorensen T, La Thangue N, Kouzarides T . Stimulation of E2F1/DP1 transcriptional activity by MDM2 oncoprotein. Nature. 1995; 375(6533):691-4. DOI: 10.1038/375691a0. View

Honda R, Tanaka H, Yasuda H . Oncoprotein MDM2 is a ubiquitin ligase E3 for tumor suppressor p53. FEBS Lett. 1998; 420(1):25-7. DOI: 10.1016/s0014-5793(97)01480-4. View

Xiao Z, Chen J, Levine A, Modjtahedi N, Xing J, Sellers W . Interaction between the retinoblastoma protein and the oncoprotein MDM2. Nature. 1995; 375(6533):694-8. DOI: 10.1038/375694a0. View

Hu Z, Jin G, Wang L, Chen F, Wang X, Shen H . MDM2 promoter polymorphism SNP309 contributes to tumor susceptibility: evidence from 21 case-control studies. Cancer Epidemiol Biomarkers Prev. 2007; 16(12):2717-23. DOI: 10.1158/1055-9965.EPI-07-0634. View

Inuzuka H, Tseng A, Gao D, Zhai B, Zhang Q, Shaik S . Phosphorylation by casein kinase I promotes the turnover of the Mdm2 oncoprotein via the SCF(beta-TRCP) ubiquitin ligase. Cancer Cell. 2010; 18(2):147-59. PMC: 2923652. DOI: 10.1016/j.ccr.2010.06.015. View

Knappskog S, Bjornslett M, Myklebust L, Huijts P, Vreeswijk M, Edvardsen H . The MDM2 promoter SNP285C/309G haplotype diminishes Sp1 transcription factor binding and reduces risk for breast and ovarian cancer in Caucasians. Cancer Cell. 2011; 19(2):273-82. DOI: 10.1016/j.ccr.2010.12.019. View

10.

Kubbutat M, Jones S, Vousden K . Regulation of p53 stability by Mdm2. Nature. 1997; 387(6630):299-303. DOI: 10.1038/387299a0. View

11.

Inuzuka H, Fukushima H, Shaik S, Wei W . Novel insights into the molecular mechanisms governing Mdm2 ubiquitination and destruction. Oncotarget. 2011; 1(7):685-690. PMC: 3248122. DOI: 10.18632/oncotarget.202. View

12.

Momand J, Wu H, Dasgupta G . MDM2--master regulator of the p53 tumor suppressor protein. Gene. 2000; 242(1-2):15-29. DOI: 10.1016/s0378-1119(99)00487-4. View

13.

Bond G, Hirshfield K, Kirchhoff T, Alexe G, Bond E, Robins H . MDM2 SNP309 accelerates tumor formation in a gender-specific and hormone-dependent manner. Cancer Res. 2006; 66(10):5104-10. DOI: 10.1158/0008-5472.CAN-06-0180. View

14.

Oliner J, Kinzler K, Meltzer P, GEORGE D, Vogelstein B . Amplification of a gene encoding a p53-associated protein in human sarcomas. Nature. 1992; 358(6381):80-3. DOI: 10.1038/358080a0. View

15.

Trotta R, Vignudelli T, Candini O, Intine R, Pecorari L, Guerzoni C . BCR/ABL activates mdm2 mRNA translation via the La antigen. Cancer Cell. 2003; 3(2):145-60. DOI: 10.1016/s1535-6108(03)00020-5. View

16.

Sheikh M, Shao Z, Hussain A, Fontana J . The p53-binding protein MDM2 gene is differentially expressed in human breast carcinoma. Cancer Res. 1993; 53(14):3226-8. View

17.

Bond G, Hu W, Bond E, Robins H, Lutzker S, Arva N . A single nucleotide polymorphism in the MDM2 promoter attenuates the p53 tumor suppressor pathway and accelerates tumor formation in humans. Cell. 2004; 119(5):591-602. DOI: 10.1016/j.cell.2004.11.022. View

18.

Economopoulos K, Sergentanis T . Differential effects of MDM2 SNP309 polymorphism on breast cancer risk along with race: a meta-analysis. Breast Cancer Res Treat. 2009; 120(1):211-6. DOI: 10.1007/s10549-009-0467-1. View

19.

Momand J, Jung D, Wilczynski S, Niland J . The MDM2 gene amplification database. Nucleic Acids Res. 1998; 26(15):3453-9. PMC: 147746. DOI: 10.1093/nar/26.15.3453. View

20.

Jones S, Roe A, Donehower L, Bradley A . Rescue of embryonic lethality in Mdm2-deficient mice by absence of p53. Nature. 1995; 378(6553):206-8. DOI: 10.1038/378206a0. View