273 IQGAP proteins in psoriasis: is it only about scaffold?

Abstract

IQGAP is a family of scaffold proteins important for the skin homeostasis. IQGAP proteins act as platforms for assembling of multiprotein complexes, coordinating the pathways of growth factor receptor signaling, cell proliferation and migration as well as epithelial-mesenchymal transition. We have found earlier the expression of the IQGAP3 to be elevated and of the IQGAP1 to be inhibited in skin of psoriasis patients. Using the gene expression profiles of lesional and nonlesional skin of psoriasis patients from the GEO database and an approach of marker graphs we have identified the protein partners of the IQGAP1 and IQGAP3 involved in psoriasis (GATA6, FOXJ2, PPARA, BHLHE41, FOXO1 and KLF15 for the IQGAP1 and POU2F2, CIC, HIC2, ERF, TEAD2, HSF1 for the IQGAP3). Thus IQGAP proteins could be involved in the pathways of immune cell differentiation into effector populations, inflammation pathways, blood vessel inflammation, keratinocyte proliferation and differentiation. According to the literature data IQGAP1 is widely expressed in human epidermis while IQGAP3 expression is restricted to the proliferative cells of the basal layer. So next we have evaluated the IQGAP3 expression under the stimulation with the psoriatic cytokines (IL-17, TNFa, IFNg) and have found it to be elevated in the inflammatory conditions. IQGAP3 inhibition itself has led to the inhibition of the expression of the proinflammatory cytokine TNFa, the antimicrobial peptides S100A8 and S100A9 and the transcription factor FRA1 (the AP1 superfamily). Further transcriptome analysis of the keratinocytes knocked-down for IQGAP3 under proinflammatory conditions will help us to identify the pathways mediated by this protein and relevant for psoriasis. The research was supported by the Russian Science Foundation (project 187500126).