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Article

Repression of exogenous gene expression by the retinoic acid target gene G0S2

  • Authors:
    • Tian Ma
    • Jessica P. Dong
    • David J. Sekula
    • Dennis Liang Fei
    • William W. Lamph
    • Michael Henderson
    • Yun Lu
    • Steven Blumen
    • Sarah J. Freemantle
    • Ethan Dmitrovsky
  • View Affiliations / Copyright

    Affiliations: Department of Pharmacology and Toxicology, Geisel School of Medicine at Dartmouth, Hanover, NH 03755, USA, Dartmouth College, Hanover, NH 03755, USA, Ligand Pharmaceutical, San Diego, CA 92121, USA
  • Pages: 1743-1753
    |
    Published online on: March 28, 2013
       https://doi.org/10.3892/ijo.2013.1876
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Abstract

The G0/G1 switch gene 2 (G0S2) is rapidly induced by all-trans-retinoic acid (RA)-treatment of acute promyelocytic leukemia (APL) and other cells. G0S2 regulates lipolysis via inhibition of adipose triglyceride lipase (ATGL). This study found that retinoic acid receptor (RAR), but not retinoid X receptor (RXR) agonists induced G0S2 expression in APL cells. Novel G0S2 functions were uncovered that included repression of exogenous gene expression and transcriptional activity. Transient G0S2 transfection repressed the activities of multiple reporter constructs (including the retinoid-regulated species RARβ, UBE1L and G0S2); this occurred in diverse cell contexts. This inhibition was antagonized by siRNA-mediated G0S2 knockdown. To determine the inhibitory effects were not due to transient G0S2 expression, G0S2 was stably overexpressed in cells without appreciable basal G0S2 expression. As expected, this repressed transcriptional activities. Intriguingly, transfection of G0S2 did not affect endogenous RARβ, UBE1L or G0S2 expression. Hence, only exogenously expressed genes were affected by G0S2. The domain responsible for this repression was localized to the G0S2 hydrophobic domain (HD). This was the same region responsible for the ability of G0S2 to inhibit ATGL activity. Whether an interaction with ATGL accounted for this new G0S2 activity was studied. Mimicking the inhibition of ATGL by oleic acid treatment that increased lipid droplet size or ATGL siRNA knockdown did not recapitulate G0S2 repressive effects. Engineered gain of ATGL expression did not rescue G0S2 transcriptional repression either. Thus, transcriptional repression by G0S2 did not depend on the ability of G0S2 to inhibit ATGL. Subcellular localization studies revealed that endogenous and exogenously-expressed G0S2 proteins were localized to the cytoplasm, particularly in the perinuclear region. Expression of a mutant G0S2 species that lacked the HD domain altered cytosolic G0S2 localization. This linked G0S2 subcellular localization to G0S2 transcriptional repression. The potential mechanisms responsible for this G0S2 repression are examined.
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1. 

Massaro D and Massaro GD: Lung development, lung function, and retinoids. New Eng J Med. 362:1829–1831. 2010. View Article : Google Scholar : PubMed/NCBI

2. 

Palczewski K: Chemistry and biology of vision. J Biol Chem. 287:1612–1619. 2012. View Article : Google Scholar : PubMed/NCBI

3. 

Pino-Lagos K, Benson MJ and Noelle RJ: Retinoic acid in the immune system. Ann NY Acad Sci. 1143:170–187. 2008. View Article : Google Scholar : PubMed/NCBI

4. 

Freemantle SJ, Spinella MJ and Dmitrovsky E: Retinoids in cancer therapy and chemoprevention: promise meets resistance. Oncogene. 22:7305–7315. 2003. View Article : Google Scholar : PubMed/NCBI

5. 

Warrell RP Jr, Frankel SR, Miller WH Jr, et al: Differentiation therapy of acute promyelocytic leukemia with tretinoin (all-trans-retinoic acid). New Eng J Med. 324:1385–1393. 1991. View Article : Google Scholar : PubMed/NCBI

6. 

Kakizuka A, Miller WH Jr, Umesono K, et al: Chromosomal translocation t(15;17) in human acute promyelocytic leukemia fuses RARα with a novel putative transcription factor, PML. Cell. 66:663–674. 1991.PubMed/NCBI

7. 

Melnick A and Licht JD: Deconstructing a disease: RARalpha, its fusion partners, and their roles in the pathogenesis of acute promyelocytic leukemia. Blood. 93:3167–3215. 1999.PubMed/NCBI

8. 

Pitha-Rowe I, Petty WJ, Kitareewan S and Dmitrovsky E: Retinoid target genes in acute promyelocytic leukemia. Leukemia. 17:1723–1730. 2003. View Article : Google Scholar : PubMed/NCBI

9. 

Kitareewan S, Blumen S, Sekula D, et al: G0S2 is an all-transretinoic acid target gene. Int J Oncol. 33:397–404. 2008.PubMed/NCBI

10. 

Tamayo P, Slonim D, Mesirov J, et al: Interpreting patterns of gene expression with self-organizing maps: methods and application to hematopoietic differentiation. Proc Natl Acad Sci USA. 96:2907–2912. 1999. View Article : Google Scholar : PubMed/NCBI

11. 

Russell L and Forsdyke D: A human putative lymphocyte G0/G1 switch gene containing a CpG-rich island encodes a small basic protein with the potential to be phosphorylated. DNA Cell Biol. 10:581–591. 1991. View Article : Google Scholar : PubMed/NCBI

12. 

Zandbergen F, Mandard S, Escher P, et al: The G0/G1 switch gene 2 is a novel PPAR target gene. Biochem J. 392:313–324. 2005. View Article : Google Scholar : PubMed/NCBI

13. 

Yang X, Lu X, Lombès M, et al: The G(0)/G(1) switch gene 2 regulates adipose lipolysis through association with adipose triglyceride lipase. Cell Metab. 11:194–205. 2010. View Article : Google Scholar : PubMed/NCBI

14. 

Cristillo AD, Heximer SP, Russell L and Forsdyke DR: Cyclosporin A inhibits early mRNA expression of G0/G1 switch (G0S2) in cultured human blood mononuclear cells. DNA Cell Biol. 16:1449–1458. 1997. View Article : Google Scholar : PubMed/NCBI

15. 

Koczan D, Guthke R, Thiesen HJ, et al: Gene expression profiling of peripheral blood mononuclear leukocytes from psoriasis patients identifies new immune regulatory molecules. Euro J Dermatol. 15:251–257. 2005.

16. 

Nakamura N, Shimaoka Y, Tougan T, et al: Isolation and expression profiling of genes upregulated in bone marrow-derived mononuclear cells of rheumatoid arthritis patients. DNA Res. 13:169–183. 2006. View Article : Google Scholar : PubMed/NCBI

17. 

Kobayashi S, Ito A, Okuzaki D, et al: Expression profiling of PBMC-based diagnostic gene markers isolated from vasculitis patients. DNA Res. 15:253–265. 2008. View Article : Google Scholar : PubMed/NCBI

18. 

Tokumaru Y, Yamashita K, Osada M, et al: Inverse correlation between cyclin A1 hypermethylation and p53 mutation in head and neck cancer identified by reversal of epigenetic silencing. Cancer Res. 64:5982–5987. 2004. View Article : Google Scholar : PubMed/NCBI

19. 

Chang X, Monitto CL, Demokan S, et al: Identification of hypermethylated genes associated with cisplatin resistance in human cancers. Cancer Res. 70:2870–2879. 2010. View Article : Google Scholar : PubMed/NCBI

20. 

Kusakabe M, Kutomi T, Watanabe K, et al: Identification of G0S2 as a gene frequently methylated in squamous lung cancer by combination of in silico and experimental approaches. Int J Cancer. 126:1895–1902. 2010.PubMed/NCBI

21. 

Kusakabe M, Watanabe K, Emoto N, et al: Impact of DNA demethylation of the G0S2 gene on the transcription of G0S2 in squamous lung cancer cell lines with or without nuclear receptor agonists. Biochem Biophys Res Commun. 390:1283–1287. 2009. View Article : Google Scholar : PubMed/NCBI

22. 

Welch C, Santra MK, El-Assaad W, et al: Identification of a protein, G0S2, that lacks Bcl-2 homology domains and interacts with and antagonizes Bcl-2. Cancer Res. 69:6782–6789. 2009. View Article : Google Scholar : PubMed/NCBI

23. 

Boyle JO, Langenfeld J, Lonardo F, et al: Cyclin D1 proteolysis: a retinoid chemoprevention signal in normal, immortalized, and transformed human bronchial epithelial cells. J Natl Cancer Inst. 91:373–379. 1999. View Article : Google Scholar

24. 

Spinella MJ, Freemantle SJ, Sekula D, Chang JH, Christie AJ and Dmitrovsky E: Retinoic acid promotes ubiquitination and proteolysis of cyclin D1 during induced tumor cell differentiation. J Biol Chem. 274:22013–22018. 1999. View Article : Google Scholar : PubMed/NCBI

25. 

Liu X, Sempere LF, Galimberti F, et al: 2009. Uncovering growth-suppressive microRNAs in lung cancer. Clin Cancer Res. 15:1177–1183. 2009. View Article : Google Scholar : PubMed/NCBI

26. 

White KA, Yore MM, Deng D and Spinella MJ: Limiting effects of RIP140 in estrogen signaling: potential mediation of anti-estrogenic effects of retinoic acid. J Biol Chem. 280:7829–7835. 2005. View Article : Google Scholar : PubMed/NCBI

27. 

Kitareewan S, Pitha-Rowe I, Sekula D, et al: UBE1L is a retinoid target that triggers PML/RARalpha degradation and apoptosis in acute promyelocytic leukemia. Proc Natl Acad Sci USA. 99:3806–3811. 2002. View Article : Google Scholar : PubMed/NCBI

28. 

Lee SB, Park JH, Woster PM, Casero RA Jr and Park MH: Suppression of exogenous gene expression by spermidine/spermine N1-acetyltransferase 1 (SSAT1) cotransfection. J Biol Chem. 285:15548–15556. 2010. View Article : Google Scholar : PubMed/NCBI

29. 

Zaiou M: Multifunctional antimicrobial peptides: therapeutic targets in several human diseases. J Mol Med. 85:317–329. 2007. View Article : Google Scholar : PubMed/NCBI

30. 

Sandgren S, Wittrup A, Cheng F, Jönsson M, Eklund E, Busch S and Belting M: The human antimicrobial peptide LL-37 transfers extracellular DNA plasmid to the nuclear compartment of mammalian cells via lipid rafts and proteoglycan-dependent endocytosis. J Biol Chem. 279:17951–17956. 2004. View Article : Google Scholar

31. 

Heckmann BL, Zhang X, Xie X and Liu J: The G0/G1 switch gene 2 (G0S2): regulating metabolism and beyond. Biochim Biophys Acta. 1831:276–281. 2013. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Ma T, Dong JP, Sekula DJ, Fei DL, Lamph WW, Henderson M, Lu Y, Blumen S, Freemantle SJ, Dmitrovsky E, Dmitrovsky E, et al: Repression of exogenous gene expression by the retinoic acid target gene G0S2. Int J Oncol 42: 1743-1753, 2013.
APA
Ma, T., Dong, J.P., Sekula, D.J., Fei, D.L., Lamph, W.W., Henderson, M. ... Dmitrovsky, E. (2013). Repression of exogenous gene expression by the retinoic acid target gene G0S2. International Journal of Oncology, 42, 1743-1753. https://doi.org/10.3892/ijo.2013.1876
MLA
Ma, T., Dong, J. P., Sekula, D. J., Fei, D. L., Lamph, W. W., Henderson, M., Lu, Y., Blumen, S., Freemantle, S. J., Dmitrovsky, E."Repression of exogenous gene expression by the retinoic acid target gene G0S2". International Journal of Oncology 42.5 (2013): 1743-1753.
Chicago
Ma, T., Dong, J. P., Sekula, D. J., Fei, D. L., Lamph, W. W., Henderson, M., Lu, Y., Blumen, S., Freemantle, S. J., Dmitrovsky, E."Repression of exogenous gene expression by the retinoic acid target gene G0S2". International Journal of Oncology 42, no. 5 (2013): 1743-1753. https://doi.org/10.3892/ijo.2013.1876
Copy and paste a formatted citation
x
Spandidos Publications style
Ma T, Dong JP, Sekula DJ, Fei DL, Lamph WW, Henderson M, Lu Y, Blumen S, Freemantle SJ, Dmitrovsky E, Dmitrovsky E, et al: Repression of exogenous gene expression by the retinoic acid target gene G0S2. Int J Oncol 42: 1743-1753, 2013.
APA
Ma, T., Dong, J.P., Sekula, D.J., Fei, D.L., Lamph, W.W., Henderson, M. ... Dmitrovsky, E. (2013). Repression of exogenous gene expression by the retinoic acid target gene G0S2. International Journal of Oncology, 42, 1743-1753. https://doi.org/10.3892/ijo.2013.1876
MLA
Ma, T., Dong, J. P., Sekula, D. J., Fei, D. L., Lamph, W. W., Henderson, M., Lu, Y., Blumen, S., Freemantle, S. J., Dmitrovsky, E."Repression of exogenous gene expression by the retinoic acid target gene G0S2". International Journal of Oncology 42.5 (2013): 1743-1753.
Chicago
Ma, T., Dong, J. P., Sekula, D. J., Fei, D. L., Lamph, W. W., Henderson, M., Lu, Y., Blumen, S., Freemantle, S. J., Dmitrovsky, E."Repression of exogenous gene expression by the retinoic acid target gene G0S2". International Journal of Oncology 42, no. 5 (2013): 1743-1753. https://doi.org/10.3892/ijo.2013.1876
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