Skip to main content
SpringerLink
Log in

IQGAP Genes in Psoriasis

  • HUMAN GENETICS
  • Published:
Russian Journal of Genetics Aims and scope Submit manuscript

Abstract

IQGAP proteins coordinate cell signaling cascades acting as scaffolds for assembly of multiprotein complexes. They mediate growth factor signaling, epithelial-mesenchymal transition, cell proliferation and migration. All of these pathways are important for the pathogenesis of psoriasis, so we suggested that the genes of the IQGAP family may play important roles in the development of this disease. qPCR analysis of the IQGAP1, IQGAP2, and IQGAP3 expression in skin of psoriasis patients showed the genes to be differentially expressed, with IQGAP1 being downregulated and IQGAP3 upregulated. Next we conducted a bioinformatic analysis of IQGAP protein partners in order to identify the protein interactions which would explain the difference between the lesional and visually nonlesional psoriatic skin. On the basis of the meta-analysis of the RNAseq data and the protein-protein interaction databases, we constructed IQGAP PPI graphs which highlighted the IQGAP protein partners involved in psoriasis. Therefore, our studies confirmed the hypothesis on the role of the IQGAP family in the pathogenesis of psoriasis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1.
Fig. 2.

Similar content being viewed by others

REFERENCES

  1. Di Meglio, P., Perera, G.K., and Nestle, F.O., The multitasking organ: recent insights into skin immune function, Immunity, 2011, vol. 35, no. 6, pp. 857—869. https://doi.org/10.1016/j.immuni.2011.12.003

    Article  CAS  PubMed  Google Scholar 

  2. Ganguly, K., Upadhyay, S., Irmler, M., and Takenaka, S., Pathway focused protein profiling indicates differential function for IL-1B, -18 and VEGF during initiation and resolution of lung inflammation evoked by carbon nanoparticle exposure in mice, Part. Fibre Toxicol., 2009, vol. 6, no. 1, p. 31. https://doi.org/10.1186/1743-8977-6-31

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Lande, R., Gregorio, J., Facchinetti, V., et al., Plasmacytoid dendritic cells sense self-DNA coupled with antimicrobial peptide, Nature, 2007, vol. 449, no. 7162, p. 564. https://doi.org/10.1038/nature06116

    Article  CAS  PubMed  Google Scholar 

  4. Capon, F., The genetic basis of psoriasis, J. Mol. Sci., 2017, vol. 18, no. 12, pii: E2526. https://doi.org/10.3390/ijms18122526

    Article  CAS  Google Scholar 

  5. Monteleon, C.L., McNeal, A., Duperret, E.K., et al., IQGAP1 and IQGAP3 serve individually essential roles in normal epidermal homeostasis and tumor progression, J. Invest. Dermatol., 2015, vol. 135, no. 9, pp. 2258—2265. https://doi.org/10.1016/j.cellsig.2009.02.023

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Johnson, M., Sharma, M., and Henderson, B.R., IQGAP1 regulation and roles in cancer, Cell. Signalling, 2009, vol. 21, no. 10, pp. 1471—1478.

    Article  CAS  PubMed  Google Scholar 

  7. Vaitheesvaran, B., Hartil, K., Navare, A., et al., Role of the tumor suppressor IQGAP2 in metabolic homeostasis: зossible link between diabetes and cancer, Metabolomics, 2014, vol. 10, no. 5, pp. 920—937. https://doi.org/10.1007/s11306-014-0639-9

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Kumar, D., Hassan, M.K., Pattnaik, N., Reduced expression of IQGAP2 and higher expression of IQGAP3 correlates with poor prognosis in cancers, PLoS One, 2017, vol. 12, no. 10. e0186977. https://doi.org/10.1371/journal.pone.0186977

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Xie, Y., Zheng, L., and Tao, L., Downregulation of IQGAP2 correlates with prostate cancer recurrence and metastasis, Transl. Oncol., 2019, vol. 12, no. 2, pp. 236—244. https://doi.org/10.1016/j.tranon.2018.10.009

    Article  PubMed  Google Scholar 

  10. Hu, G., Xu, Y., Chen, W., et al., RNA interference of IQ motif containing GTPase-activating protein 3 (IQGAP3) inhibits cell proliferation and invasion in breast carcinoma cells, Oncol. Res., 2016, vol. 24, no. 6, pp. 455—461. https://doi.org/10.3727/096504016X14685034103635

    Article  PubMed  PubMed Central  Google Scholar 

  11. Wang, S., Watanabe, T., Noritake, J., et al., IQGAP3, a novel effector of Rac1 and Cdc42, regulates neurite outgrowth, J. Cell Sci., 2007, vol. 120, no. 4, pp. 567—577. https://doi.org/10.1242/jcs.03356

    Article  CAS  PubMed  Google Scholar 

  12. McNulty, D.E., Li, Z., White, C.D., et al., Map kinase scaffold IQGAP1 binds the EGF receptor and modulates its activation, J. Biol. Chem., 2011, pp. 15010—15021. https://doi.org/10.1074/jbc.M111.227694

  13. White, C.D., Erdemir, H.H., and Sacks, D.B., IQGAP1 and its binding proteins control diverse biological functions, Cell. Signalling, 2012, vol. 24, no. 4, pp. 826—834. https://doi.org/10.1016/j.cellsig.2011.12.005

    Article  CAS  PubMed  Google Scholar 

  14. Watanabe, T., Wang, S., and Kaibuchi, K., IQGAPs as key regulators of actin—cytoskeleton dynamics, Cell Struct. Funct., 2015, vol. 40, no. 2, pp. 69—77. https://doi.org/10.1247/csf.15003

    Article  CAS  PubMed  Google Scholar 

  15. Livak, K.J. and Schmittgen, T.D., Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method, Methods, 2001, vol. 25, no. 4, pp. 402—408. https://doi.org/10.1006/meth.2001.1262

    Article  CAS  PubMed  Google Scholar 

  16. Cock, P.J.A., Fields, C.J., Goto, N., The Sanger FASTQ file format for sequences with quality scores, and the Solexa/Illumina FASTQ variants, Nucleic Acids Res., 2009, vol. 38, no. 6, pp. 1767—1771. https://doi.org/10.1093/nar/gkp1137

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Bolger, A.M., Lohse, M., and Usadel, B., Trimmomatic: a flexible trimmer for Illumina sequence data, Bioinformatics, 2014, vol. 30, no. 15, pp. 2114—2120. https://doi.org/10.1093/bioinformatics/btu170

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Dobin, A., Davis, C.A., Schlesinger, F., and Drenkow, J., STAR: ultrafast universal RNA-seq aligner, Bioinformatics, 2013, vol. 29, no. 1, pp. 15—21. https://doi.org/10.1093/bioinformatics/bts635

    Article  CAS  PubMed  Google Scholar 

  19. Szklarczyk, D., Franceschini, A., Kuhn, M., et al., The STRING database in 2011: functional interaction networks of proteins, globally integrated and scored, Nucleic Acids Res., 2010, vol. 39, suppl. 1, pp. D561—D568. https://doi.org/10.1093/nar/gkq973

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Han, W.S., Lee, J., Pham, M.D., and Yu, J.X., iGraph: a framework for comparisons of disk-based graph indexing techniques, Proc. VLDB Endowment, 2010, vol. 3. nos. 1—2, pp. 449—459. https://doi.org/10.14778/1920841.1920901

  21. Chuang, H.Y., Lee, E., Liu, Y.T., et al., Network-based classification of breast cancer metastasis, Mol. Syst. Biol., 2007, vol. 3, no. 1, p. 140. https://doi.org/10.1038/msb4100180

    Article  PubMed  PubMed Central  Google Scholar 

  22. Skovorodnikova, P.A., Chesnokov, M.S., Budko, A.A., et al., Scaffold proteins of the IQGAP family—multifunctional regulators of intracellular signaling and tumor transformation, Usp. Mol. Onkol., 2017, vol. 4, no. 2.

  23. Hedman, A.C., Smith, J.M., and Sacks, D.B., The biology of IQGAP proteins: beyond the cytoskeleton, EMBO Rep., 2015, vol. 16, no. 4, pp. 427—446.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Buttrick, T.S., Wang, W., Yung, C., et al., Foxo1 promotes Th9 cell differentiation and airway allergy, Sci. Rep., 2018, vol. 8, no. 1, p. 818. https://doi.org/10.4049/jimmunol.1500849

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Eberle, F.C., Bruck, J., Holstein, J., et al., Recent advances in understanding psoriasis version 1, F1000Res, 2016, vol. 5. https://doi.org/10.12688/f1000research.7927.1

  26. Pandey, D., Berkowitz, D., and Romer, L., Kruppel-like factor 15: a critical transcriptional regulator of hypoxia induced endothelial arginase 2, FASEB J., 2016, vol. 30, no. 11, suppl. 1.

  27. Mehta, N.N., Shin, D.B., Joshi, A.A., et al., Effect of 2 psoriasis treatments on vascular inflammation and novel inflammatory cardiovascular biomarkers: a randomized placebo-controlled trial, Circ. Cardiovasc. Imaging, 2018, vol. 11, no. 6. e007394. https://doi.org/10.1161/CIRCIMAGING.117.007394

    Article  PubMed  PubMed Central  Google Scholar 

  28. Jain, M.K., Sangwung, P., and Hamik, A., Regulation of an inflammatory disease: Krüppel-like factors and atherosclerosis, Arterioscler. Thromb. Vasc. Biol., 2014, vol. 34, no. 3, pp. 499—508. https://doi.org/10.1161/ATVBAHA.113.301925

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Dubrac, S. and Schmuth, M., PPAR-alpha in cutaneous inflammation, Dermatoendocrinology, 2011, vol. 3, no. 1, pp. 23—26. https://doi.org/10.4161/derm.3.1.14615

    Article  CAS  Google Scholar 

  30. Carrera, M., Bitu, C.C., de Oliveira, C.E., et al., HOXA10 controls proliferation, migration and invasion in oral squamous cell carcinoma, Int. J. Clin. Exp. Pathol., 2015, vol. 8, no. 4, p. 3613.

    CAS  PubMed  PubMed Central  Google Scholar 

  31. Zolotarenko, A., Chekalin, E., Piruzian, E., and Bruskin, S., FRA1 mediates the activation of keratinocytes: implications for the development of psoriatic plaques, Biochim. Biophys. Acta Mol. Basis Dis., 2018, vol. 1864, no. 12, pp. 3726—3734. https://doi.org/10.1016/j.bbadis.2018.09.016

    Article  CAS  PubMed  Google Scholar 

  32. Brandner, J.M., Zorn-Kruppa, M., Yoshida, T., et al., Epidermal tight junctions in health and disease, Tissue Barriers, 2015, vol. 3, nos. 1—2. e974451. https://doi.org/10.4161/21688370.2014.974451

    Article  CAS  PubMed  Google Scholar 

  33. Collin, M., Dickinson, R., and Bigley, V., Haematopoietic and immune defects associated with GATA2 mutation, Br. J. Haematol., 2015, vol. 169, no. 2, pp. 173—187. https://doi.org/10.1111/bjh.13317

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Qasim, M., Rahman, H., Oellerich, M., and Asif, A.R., Differential proteome analysis of human embryonic kidney cell line (HEK-293) following mycophenolic acid treatment, Proteome Sci., 2011, vol. 9, no. 1, p. 57. https://doi.org/10.1161/01.ATV.0000126373.52450.32

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Kunimoto, K., Nojima, H., Yamazaki, Y., and Yoshikawa, T., Involvement of IQGAP3, a regulator of Ras/ERK-related cascade, in hepatocyte proliferation in mouse liver regeneration and development, J. Cell. Physiol., 2009, vol. 220, no. 3, pp. 621—631. https://doi.org/10.1002/jcp.21798

    Article  CAS  PubMed  Google Scholar 

  36. Yang, Y., Zhao, W., Xu, Q.W., et al., IQGAP3 promotes EGFR-ERK signaling and the growth and metastasis of lung cancer cells, PLoS One, 2014, vol. 9, no. 5. e97578. https://doi.org/10.1371/journal.pone.0097578

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Shi, Y., Qin, N., Zhou, Q., et al., Role of IQGAP3 in metastasis and epithelial–mesenchymal transition in human hepatocellular carcinoma, J. Translat. Med., 2017, vol. 15, no. 1, p. 176. https://doi.org/10.1186/s12967-017-1275-8

    Article  CAS  Google Scholar 

Download references

Funding

This study was funded by a grant from the Russian Science Foundation (project no. 18-75-00126, supervisor A.D. Zolotarenko).

Author information

Authors and Affiliations

  1. Vavilov Institute of General Genetics, Russian Academy of Sciences, 119991, Moscow, Russia

    E. V. Chekalin, A. D. Zolotarenko & S. A. Bruskin

  2. Moscow Institute of Physics and Technology, 141701, Dolgoprudny, Moscow oblast, Russia

    E. V. Chekalin

Authors
  1. E. V. Chekalin
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. A. D. Zolotarenko
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. S. A. Bruskin
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Authors A.D. Zolotarenko and S.A. Bruskin formulated the idea of research and developed an experiment, E.V. Chekalin conducted a meta-analysis and construction of graphs of protein-protein interactions, A.D. Zolotarenko assessed the accumulation of transcripts in biopsies. A.D. Zolotarenko and E.V. Chekalin participated in data processing. All authors participated in the writing of the text of the article and in the discussion of the results.

Corresponding author

Correspondence to A. D. Zolotarenko.

Ethics declarations

Conflict of interest. The authors declare that they have no conflict of interest.

Statement of compliance with standards of research involving humans as subjects. The study was approved by the Local Ethics Committee at the Institute of General Genetics of the Russian Academy of Sciences and complies with the principles set forth in the Declaration of the Helsinki Agreement of 1964 and its subsequent changes or comparable ethical standards. All patients signed informed voluntary consent forms.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Chekalin, E.V., Zolotarenko, A.D. & Bruskin, S.A. IQGAP Genes in Psoriasis. Russ J Genet 56, 345–353 (2020). https://doi.org/10.1134/S1022795420030047

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1134/S1022795420030047

Keywords:

Search

Navigation