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ETS-Domain Transcription Factor Elk1 is Critical for Embryo Implantation via Regulatory Control on Superoxide Dismutase 1 (SOD1) .
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Mitogen Activated Protein Kinase (MAPK) signaling is one of the decisive pathways in regulating embryo-uterine interactions. Ras-MAP Kinase activation is effected by ETS family proteins; ELK1, being the first member of the Ternary Complex Factor (TCF) family, is rapidly activated by ERK. Based on the significance of ETS family member in the process of embryo implantation and presence of ELK1 during embryogenesis, we hypothesized that ELK1 would also discharge its role in embryo implantation. We intend to analyze the importance of ELK1 during embryo implantation for which we have used a mouse pregnancy model system. Our results clearly document the expression of ELK1 during different days of pregnancy. ELK1 is highly activated during peri-implantation period as its expression in the nucleus is increased compared to pre-implantation stages. Elk-1 knock down leads to pregnancy failure which is attributed to changes in perforin, c-fos, Mcl-1 and Sod1. Elk-1 also decreases SOD activity which is the crucial factor controlling superoxide during embryo implantation. These results suggest that Elk-1 affects the process of embryo attachment to uterus either directly or by way of molecules that are obligatory for the process of embryo implantation.
Keywords
Elk-1, Embryo Implantation, SOD1, SOD Activity
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- Norwitz ER, Schust DJ, Fisher SJ. Implantation and the survival of early pregnancy. New England Journal of Medicine. 2001; 345(19):1400–8. https://doi.org/10.1056/NEJMra000763. PMid:11794174
- Sengupta J, Ghosh D. Role of progesterone on peri-implantation stage endometrium-embryo interaction in the primate. Steroids. 2000; 65(10–11):753–62. https://doi.org/10.1016/S0039-128X(00)00191-4
- Dey SK, Lim H, Das SK, et al. Molecular cues to implantation. Endocrine Reviews. 2004; 25(3):341–73. https://doi.org/10.1210/ er.2003-0020. PMid:15180948
- Oikawa T, Yamada T, Molecular biology of the Ets family of transcription factors. Gene. 2003; 303:11–34. https://doi.org/10.1016/ S0378-1119(02)01156-3
- Koo SH, Flechner L, Qi L, et al. The CREB coactivator TORC2 is a key regulator of fasting glucose metabolism, Nature. 2005; 437(7062):1109–11. https://doi.org/10.1038/nature03967. PMid:16148943
- Bartel F, Higuchi T, Spyropoulos D. Mouse models in the study of the Ets family of transcription factors. Oncogene. 2000; 19(55):6443–54. https://doi.org/10.1038/sj.onc.1204038. PMid:11175360
- Shao N, Chai Y, Cui JQ, et al. Induction of apoptosis by Elk-1 and deltaElk-1 proteins. Oncogene. 1998; 17(4):527–32. https://doi. org/10.1038/sj.onc.1201931. PMid:9696047
- Li J, Shiroyanagi Y, Lin G, et al. Serum response factor, its cofactors, and epithelial-mesenchymal signaling in urinary bladder smooth muscle formation. Differentiation. 2006; 74(1):30–9. https://doi.org/10.1111/j.1432-0436.2006.00057.x. PMid:16466398
- Smith ER, Smedberg JL, Rula ME, et al. Disassociation of MAPK activation and c-Fos expression in F9 embryonic carcinoma cells following retinoic acid-induced endoderm differentiation. Journal of Biological Chemistry. 2001; 276(34):32094–100. https://doi. org/10.1074/jbc.M105009200. PMid:11402055
- Nautiyal J, Kumar PG, Laloraya M. 17Beta-estradiol induces nuclear translocation of CrkL at the window of embryo implantation. Biochemical and Biophysical Research Communications. 2004; 318(1):103–12. https://doi.org/10.1016/j.bbrc.2004.04.005. PMid:15110759
- Shen J, Samul R, Silva RL, et al. Suppression of ocular neovascularization with siRNA targeting VEGF receptor 1. Gene Therapy. 2006; 13(3):225–34. https://doi.org/10.1038/sj.gt.3302641. PMid:16195704
- Vanhoutte P, Nissen JL, Brugg B, et al. Opposing roles of Elk-1 and its brain-specific isoform, short Elk-1, in nerve growth factorinduced PC12 differentiation. Journal of Biological Chemistry. 2001; 276(7):5189–96. https://doi.org/10.1074/jbc.M006678200. PMid:11050086
- Kel A, Voss N, Jauregui R, et al. Beyond microarrays: find key transcription factors controlling signal transduction pathways. BMC Bioinformatics. 2006; 7 Suppl 2:S13. https://doi.org/10.1186/1471-2105-7-S2-S13. PMid:17118134. PMCid:PMC1683568
- Townsend KJ, Zhou P, Qian L, et al. Regulation of MCL1 through a serum response factor/Elk-1-mediated mechanism links expression of a viability-promoting member of the BCL2 family to the induction of hematopoietic cell differentiation. Journal of Biological Chemistry. 1999; 274(3):1801–13. https://doi.org/10.1074/jbc.274.3.1801. PMid:9880563
- Demir O, Aysit N, Onder Z, et al. ETS-domain transcription factor Elk-1 mediates neuronal survival: SMN as a potential target.Biochimica et Biophysica Acta. 2011; 1812(6):652–62. https://doi.org/10.1016/j.bbadis.2011.02.012. PMid:21362474
- Chang MS, Yoo HY, Rho HM. Positive and negative regulatory elements in the upstream region of the rat Cu/Zn-superoxide dismutase gene. Biochemical Journal. 1999; 339( Pt 2):335–41. https://doi.org/10.1042/bj3390335. PMid:10191264. PMCid:PMC1220162
- Sharrocks. Complexities in ETS-domain transcription factor function and regulation: Lessons from the TCF (ternary complex factor) subfamily. Biochemical Society Transactions. 2002; 30(2):1–9. https://doi.org/10.1042/bst0300001. PMid:12023815
- Prise I, Sharrocks AD. ELK1 has a dual activating and repressive role in human embryonic stem cells. Wellcome Open Research. 2019; 4:41. https://doi.org/10.12688/wellcomeopenres.15091.1. PMid:31346550 PMCid:PMC6619381
- Maekawa M, Yamamoto T, Kohno M, et al. Requirement for ERK MAP kinase in mouse preimplantation development. Development. 2007; 134(15): 2751–9. https://doi.org/10.1242/dev.003756. PMid:17611221
- Banerjee P, Sapru K, Strakova Z, Fazleabas AT. Chorionic gonadotropin regulates prostaglandin E synthase via a phosphatidylinositol 3-kinase-extracellular regulatory kinase pathway in a human endometrial epithelial cell line: implications for endometrial responses for embryo implantation, Endocrinology. 2009; 150(9):4326–37. https://doi.org/10.1210/en.2009-0394. PMid:19556419.
- PMCid:PMC2736085
- Chang BD, Xuan Y, Broude H, et al. Role of p53 and p21waf1/cip1 in senescence-like terminal proliferation arrest induced in human tumor cells by chemotherapeutic drugs. Oncogene. 1999; 18(34):4808–18. https://doi.org/10.1038/sj.onc.1203078. PMid:10490814
- Treisman R. Regulation of transcription by MAP kinase cascades. Current Opinion in Cell Biology.1996; 8(2):205–15. https://doi. org/10.1016/S0955-0674(96)80067-6
- Booy EP, Henson ES, Gibson SB, Epidermal growth factor regulates Mcl-1 expression through the MAPK-Elk-1 signalling pathway contributing to cell survival in breast cancer. Oncogene. 2011; 30(20):2367–78. https://doi.org/10.1038/onc.2010.616. PMid:21258408. PMCid:PMC3145838
- Rinkenberger JL, Horning S, Klocke B, et al. Mcl-1 deficiency results in peri-implantation embryonic lethality. Genes & Development. 2000; 14(1):23–7. https://doi.org/10.1101/gad.14.1.23. PMid:10640272. PMCid:PMC316347
- Tian X, Zhang L, Wu Y. [Perforin protein and gene expression in the different phases of endometrium]. Zhonghua Fu Chan Ke Za Zhi. 1998; 33(10):591–3.
- Schmidt NW, Khanolkar A, Hancox L, et al. Perforin plays an unexpected role in regulating T-cell contraction during prolonged Listeria monocytogenes infection. European Journal of Immunology. 42(3):629–40. https://doi.org/10.1002/eji.201141902. PMid:22161269. PMCid:PMC3418886
- Youn BS, Kim KK, Kwon BS. A critical role of Sp1- and Ets-related transcription factors in maintaining CTL-specific expression of the mouse perforin gene. Journal of Immunology. 1996; 157(8):3499–509.
- Laloraya M, Kumar GP, Laloraya MM. A possible role of superoxide anion radical in the process of blastocyst implantation in Mus musculus. Biochemical and Biophysical Research Communications. 1989; 161(2):762–70. https://doi.org/10.1016/0006291X(89)92665-X .
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