What Can Study of Oligomerization of Proteinsin the Process of Oncogenesis Bring Us?

Česká verzia

Authors: D. Coufalová; B. Vojtěšek; L. Hernychová
Authors place of work: Regionální centrum aplikované molekulární onkologie, Masarykův onkologický ústav, Brno
Published in the journal: Klin Onkol 2015; 28(Supplementum 2): 6-10
doi: https://doi.org/10.14735/amko20152S6

Summary

Many cellular proteins form oligomers. The equilibrium between monomeric and oligomeric states of these proteins is important for the regulation of protein activity. Modulation of the oligomerization equilibrium could be an interesting approach in the development of new therapeutic agents. This review summarizes information about protein oligomerization and modulation of this process, demonstrating the role of oligomerization in oncogenesis by tumor suppressor protein p53, which forms tetrameric structure. Today, many studies focus on finding compounds that stabilize its tetramers. Among the methods for studying oligomerization, we present hydrogen/ deuterium exchange method coupled with mass spectrometry which is suitable for the detection of protein‑protein interaction and analysis of oligomerization dynamics.

Key words:
proteomics – drug design – tumor suppressor protein p53 – oligomerization – hydrogen/ deuterium exchange

This study was supported by the European Regional Development Fund and the State Budget of the Czech Republic (RECAMO, CZ.1.05/2.1.00/03.0101), MEYS – NPS I – LO1413, MH CZ – DRO (MMCI, 00209805) and BBMRI_CZ (LM2010004).

The authors declare they have no potential confl icts of interest concerning drugs, products, or services used in the study.

The Editorial Board declares that the manuscript met the ICMJE “uniform requirements” for biomedical papers.

Submitted:
9. 4. 2015

Accepted:
15. 6. 2015

Zdroje

1. Ali MH, Imperiali B. Protein oligomerization: how and why. Bioorganic Med Chem 2005; 13(17): 5013– 5020.

2. Goodsell DS, Olson AJ. Structural symmetry and protein function. Annu Rev Biophys Biomol Struct 2000; 29: 105– 153.

3. Koshland DE, Némethy G, Filmer D. Comparison of experimental binding data and theoretical models in proteins containing subunits. Biochemistry 1966; 5(1): 365– 385.

4. Jaffe EK. Morpheeins – a new structural paradigm for allosteric regulation. Trends Biochem Sci 2005; 30(9): 490– 497.

5. Jaffe EK, Lawrence SH. Allostery and the dynamic oligomerization of porphobilinogen synthase. Arch Biochem Biophys 2012; 519(2): 144– 153. doi: 10.1016/ j.abb.2011.10.010.

6. Selwood T, Jaffe EK. Dynamic dissociating homo‑ oligomers and the control of protein function. Arch Biochem Biophys 2012; 519(2): 131– 143. doi: 10.1016/ j.abb.2011.11.020.

7. Šmardová J, Koptíková J. Brazilský příběh mutace p53 R337H. Klin Onkol 2014; 27(4): 247– 254. doi: 10.14735/amko2014247.

8. Kitayner M, Rozenberg H, Kessler N et al. Structural basis of DNA recognition by p53 tetramers. Mol Cell 2006; 22(6): 741– 753.

9. Kawaguchi T, Kato S, Otsuka K et al. The relationship among p53 oligomer formation, structure and transcriptional activity using a comprehensive missense mutation library. Oncogene 2005; 24(46): 6976– 6981.

10. Olivier M, Eeles R, Hollstein M et al. The IARC TP53 database: new online mutation analysis and recommendations to users. Hum Mutat 2002; 19(6): 607– 614.

11. Stommel JM, Marchenko ND, Jimenez GS et al. A leucine‑ rich nuclear export signal in the p53 tetramerization domain: regulation of subcellular localization and p53 activity by NES masking. EMBO J 1999; 18(6): 1660– 1672.

12. Salvatella X, Martinell M, Gairí M et al. A tetraguanidinium ligand binds to the surface of the tetramerization domain of protein p53. Angew Chem Int Ed Engl 2004; 43(2): 196– 198.

13. Martinell M, Salvatella X, Fernández‑ Carneado J et al. Synthetic ligands able to interact with the p53 tetramerization domain. Towards understanding a protein surface recognition event. Chembiochem 2006; 7(7): 1105– 1113.

14. Kamada R, Yoshino W, Nomura T et al. Enhancement of transcriptional activity of mutant p53 tumor suppressor protein through stabilization of tetramer formation by calix[6]arene derivatives. Bioorg Med Chem Lett 2010; 20(15): 4412– 4415. doi: 10.1016/ j.bmcl.2010.06.053.

15. Gabizon R, Brandt T, Sukenik S et al. Specific recognition of p53 tetramers by peptides derived from p53 interacting proteins. PLoS One 2012; 7(5): e38060. doi: 10.1371/ journal.pone.0038060.

16. Gray TA, Murray E, Nowicki MW et al. Development of a fluorescent monoclonal antibody‑based assay to measure the allosteric effects of synthetic peptides on self‑ oligomerization of AGR2 protein. Protein Sci 2013; 22(9): 1266– 1278. doi: 10.1002/ pro.2299.

17. Graves B, Thompson T, Xia M et al. Activation of the p53 pathway by small‑molecule‑induced MDM2 and MDMX dimerization. Proc Natl Acad Sci U S A 2012; 109(29): 11788– 11793. doi: 10.1073/ pnas.1203789109.

18. Anastasiou D, Yu Y, Israelsen WJ et al. Pyruvate kinase M2 activators promote tetramer formation and suppress tumorigenesis. Nat Chem Biol 2012; 8(10): 839– 847.

19. Miller GD, Woessner DW, Sirch MJ et al. Multidomain targeting of Bcr‑ Abl by disruption of oligomerization and tyrosine kinase inhibition: toward eradication of CML. Mol Pharm 2013; 10(9): 3475– 3483. doi: 10.1021/ mp400323c.

20. He MM, Smith AS, Oslob JD et al. Small‑molecule inhibition of TNF‑alpha. Science 2005; 310(5750): 1022– 1025.

21. Teufel DP, Freund SM, Bycroft M et al. Four domains of p300 each bind tightly to a sequence spanning both transactivation subdomains of p53. Proc Natl Acad Sci U S A 2007; 104(17): 7009– 7014.

22. Rowinsky EK. The development and clinical utility of the taxane class of antimicrotubule chemotherapy agents. Annu Rev Med 1997; 48: 353– 374.

23. Mitra A, Sept D. Taxol allosterically alters the dynamics of the tubulin dimer and increases the flexibility of microtubules. Biophys J 2008; 95(7): 3252– 3258. doi: 10.1529/ biophysj.108.133884.

24. Xiao H, Verdier‑ Pinard P, Fernandez‑ Fuentes N et al.Insights into the mechanism of microtubule stabilization by Taxol. Proc Natl Acad Sci U S A 2006; 103(27): 10166– 10173.

25. Gabizon R, Friedler A. Allosteric modulation of protein oligomerization: an emerging approach to drug design. Front Chem 2014; 2(9): 1– 15. doi: 10.3389/ fchem.2014.00009.

26. Veldkamp CT, Seibert C, Peterson FC et al. Structural basis of CXCR4 sulfotyrosine recognition by the chemokine SDF‑ 1/ CXCL12. Sci Signal 2008; 1(37): ra4. doi: 10.1126/ scisignal.1160755.

27. Lee CC, Lin TW, Ko TP et al. The hexameric structures of human heat shock protein 90. PLoS One 2011; 6(5): e19961. doi: 10.1371/ journal.pone.0019961.

28. Aprile FA, Dhulesia A, Stengel F et al. Hsp70 oligomerization is mediated by an interaction between the interdomain linker and the substrate‑binding domain. PLoS One 2013; 8(6): e67961. doi: 10.1371/ journal.pone.0067961.

29. Hamuro Y, Coales SJ, Southern MR et al. Rapid analysis of protein structure and dynamics by hydrogen/ deuterium exchange mass spectrometry. J Biomol Tech 2003; 14(3): 171– 182.

30. Dempsey CE. Hydrogen exchange in peptides and proteins using NMR spectroscopy. Prog Nucl Magn Reson Spectrosc 2001; 39(2): 135– 170.

31. Hvidt A, Nielsen SO. Hydrogen exchange in proteins. Adv Protein Chem 1966; 21: 287– 386.

32. Wales TE, Eggertson MJ, Engen JR. Mass spectrometry data analysis in proteomics. Methods Mol Biol 2013; 1007: 263– 288.

33. Paslawski W, Mysling S, Thomsen K et al. Co‑ existence of two different α‑ synuclein oligomers with different core structures determined by hydrogen/ deuterium exchange mass spectrometry. Angew Chem Int Ed Engl 2014; 53(29): 7560– 7563. doi: 10.1002/ anie.201400491.

34. Mobley JA, Poliakov A. Detection of early unfolding events in a dimeric protein by amide proton exchange and native electrospray mass spectrometry. Protein Sci 2009; 18(8): 1620– 1627. doi: 10.1002/pro.176.