The Expression of B23 and EGR1 Proteins is Functionally Linked in Tumor Cells Under Stress Conditions

Overview

Journal BMC Cell Biol

Publisher Biomed Central

Specialty Cell Biology

Date 2015 Nov 19

PMID 26577150

Citations 6

Authors

Donatella Ponti

Daniela Bastianelli

Paolo Rosa

Luca Pacini

Mohsen Ibrahim

Erino Angelo Rendina

Giuseppe Ragona

Antonella Calogero

Affiliations

Soon will be listed here.

Abstract

Background: The nucleolus is a multi-domain enriched with proteins involved in ribosome biogenesis, cell cycle and apoptosis control, viral replication and differentiation of stem cells. Several authors have suggested a role for the nucleolus also in malignant transformation. We have recently demonstrated that under specific circumstances the transcriptional factor EGR1 is shuttled to the nucleolus where it functions as a negative regulator of RNA polymerase I. Since this activity is hampered in ARF -/- cells, and ARF transcription is regulated by EGR1 while the turnover of ARF protein is under the control of B23, we speculated that some sort of cooperation between EGR1 and B23 might also exist.

Results: In this work we identified a canonical EGR1 binding site on the B23 promoter through experiments of transactivation and in vitro DNA binding assay. We then found that the levels of B23 expression are directly correlated with those of EGR1, and that this correlation applies to several cellular types and to different stress conditions. Furthermore, we showed that EGR1 stability and accumulation within the nucleolus is in turn regulated by B23 through proteasome involvement, similarly to ARF turnover.

Conclusion: Our results highlight EGR1 as a regulator of B23 expression actively playing within the newly discovered nucleolar B23-ARF-EGR1 network.

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References

Valdez B, Perlaky L, Henning D, Saijo Y, Chan P, Busch H . Identification of the nuclear and nucleolar localization signals of the protein p120. Interaction with translocation protein B23. J Biol Chem. 1994; 269(38):23776-83. View

Paron I, DElia A, DAmbrosio C, Scaloni A, DAurizio F, Prescott A . A proteomic approach to identify early molecular targets of oxidative stress in human epithelial lens cells. Biochem J. 2003; 378(Pt 3):929-37. PMC: 1224035. DOI: 10.1042/BJ20031190. View

Bertwistle D, Sugimoto M, Sherr C . Physical and functional interactions of the Arf tumor suppressor protein with nucleophosmin/B23. Mol Cell Biol. 2004; 24(3):985-96. PMC: 321449. DOI: 10.1128/MCB.24.3.985-996.2004. View

Pacini L, Suffredini S, Ponti D, Coppini R, Frati G, Ragona G . Altered calcium regulation in isolated cardiomyocytes from Egr-1 knock-out mice. Can J Physiol Pharmacol. 2013; 91(12):1135-42. DOI: 10.1139/cjpp-2012-0419. View

Virolle T, Adamson E, Baron V, Birle D, Mercola D, Mustelin T . The Egr-1 transcription factor directly activates PTEN during irradiation-induced signalling. Nat Cell Biol. 2002; 3(12):1124-8. DOI: 10.1038/ncb1201-1124. View

Kamijo T, Weber J, Zambetti G, Zindy F, Roussel M, Sherr C . Functional and physical interactions of the ARF tumor suppressor with p53 and Mdm2. Proc Natl Acad Sci U S A. 1998; 95(14):8292-7. PMC: 20969. DOI: 10.1073/pnas.95.14.8292. View

Yao Z, Duan S, Hou D, Wang W, Wang G, Liu Y . B23 acts as a nucleolar stress sensor and promotes cell survival through its dynamic interaction with hnRNPU and hnRNPA1. Oncogene. 2010; 29(12):1821-34. DOI: 10.1038/onc.2009.473. View

Dingwall C, Dilworth S, Black S, Kearsey S, Cox L, Laskey R . Nucleoplasmin cDNA sequence reveals polyglutamic acid tracts and a cluster of sequences homologous to putative nuclear localization signals. EMBO J. 1987; 6(1):69-74. PMC: 553358. DOI: 10.1002/j.1460-2075.1987.tb04720.x. View

Colombo E, Bonetti P, Denchi E, Martinelli P, Zamponi R, Marine J . Nucleophosmin is required for DNA integrity and p19Arf protein stability. Mol Cell Biol. 2005; 25(20):8874-86. PMC: 1265791. DOI: 10.1128/MCB.25.20.8874-8886.2005. View

10.

Colombo E, Marine J, Danovi D, Falini B, Pelicci P . Nucleophosmin regulates the stability and transcriptional activity of p53. Nat Cell Biol. 2002; 4(7):529-33. DOI: 10.1038/ncb814. View

11.

Liu C, Yao J, de Belle I, Huang R, Adamson E, Mercola D . The transcription factor EGR-1 suppresses transformation of human fibrosarcoma HT1080 cells by coordinated induction of transforming growth factor-beta1, fibronectin, and plasminogen activator inhibitor-1. J Biol Chem. 1999; 274(7):4400-11. DOI: 10.1074/jbc.274.7.4400. View

12.

de Belle I, Huang R, Fan Y, Liu C, Mercola D, Adamson E . p53 and Egr-1 additively suppress transformed growth in HT1080 cells but Egr-1 counteracts p53-dependent apoptosis. Oncogene. 1999; 18(24):3633-42. DOI: 10.1038/sj.onc.1202696. View

13.

Snyder-Keller A, Chandra R, Lin Y, Mitchell E . Basal EGR-1 (zif268, NGFI-A, Krox-24) expression in developing striatal patches: role of dopamine and glutamate. Brain Res. 2002; 958(2):297-304. DOI: 10.1016/s0006-8993(02)03602-8. View

14.

Itahana K, Bhat K, Jin A, Itahana Y, Hawke D, Kobayashi R . Tumor suppressor ARF degrades B23, a nucleolar protein involved in ribosome biogenesis and cell proliferation. Mol Cell. 2003; 12(5):1151-64. DOI: 10.1016/s1097-2765(03)00431-3. View

15.

Korgaonkar C, Hagen J, Tompkins V, Frazier A, Allamargot C, Quelle F . Nucleophosmin (B23) targets ARF to nucleoli and inhibits its function. Mol Cell Biol. 2005; 25(4):1258-71. PMC: 548001. DOI: 10.1128/MCB.25.4.1258-1271.2005. View

16.

Ciarmatori S, Scott P, Sutcliffe J, McLees A, Alzuherri H, Dannenberg J . Overlapping functions of the pRb family in the regulation of rRNA synthesis. Mol Cell Biol. 2001; 21(17):5806-14. PMC: 87300. DOI: 10.1128/MCB.21.17.5806-5814.2001. View

17.

Yung B, BUSCH R, Busch H, MAUGER A, Chan P . Effects of actinomycin D analogs on nucleolar phosphoprotein B23 (37,000 daltons/pI 5.1). Biochem Pharmacol. 1985; 34(22):4059-63. DOI: 10.1016/0006-2952(85)90387-9. View

18.

Huang R, Fan Y, de Belle I, Niemeyer C, Gottardis M, Mercola D . Decreased Egr-1 expression in human, mouse and rat mammary cells and tissues correlates with tumor formation. Int J Cancer. 1997; 72(1):102-9. DOI: 10.1002/(sici)1097-0215(19970703)72:1<102::aid-ijc15>3.0.co;2-l. View

19.

Calogero A, Lombari V, De Gregorio G, Porcellini A, Ucci S, Arcella A . Inhibition of cell growth by EGR-1 in human primary cultures from malignant glioma. Cancer Cell Int. 2004; 4(1):1. PMC: 324562. DOI: 10.1186/1475-2867-4-1. View

20.

Gao H, Jin S, Song Y, Fu M, Wang M, Liu Z . B23 regulates GADD45a nuclear translocation and contributes to GADD45a-induced cell cycle G2-M arrest. J Biol Chem. 2005; 280(12):10988-96. DOI: 10.1074/jbc.M412720200. View