Absence of a Human DnaJ Protein hTid-1S Correlates with Aberrant Actin Cytoskeleton Organization in Lesional Psoriatic Skin

Background: HSP27 phosphorylation plays pivotal roles on F-actin polymerization and actin cytoskeleton organization. Results: The loss of hTid-1S expression was observed in lesional human psoriatic skin. Conclusion: The binding of hTid-1S with MK5 inhibits HSP27 phosphorylation and attenuates F-actin polymerization. Significance: The lack of hTid-1S expression correlates with the aberrant actin cytoskeleton organization in psoriatic human skin. The biochemical mechanism by which the human tumorous imaginal disc1S (hTid-1S) interferes with actin cytoskeleton organization in keratinocytes of human skin epidermis was investigated. We found that hTid-1, specifically hTid-1S, interacts with MK5, a p38-regulated/activated protein kinase, and inhibits the protein kinase activity of MK5 that phosphorylates heat shock protein HSP27 in cultured HeLa cells. Thus, hTid-1S expression inhibits the phosphorylation of HSP27 known to play important roles in F-actin polymerization and actin cytoskeleton organization. The interplay between MK5/HSP27 signaling and hTid-1S expression was supported by the inhibition of HSP27 phosphorylation and MK5 activity in HeLa cells in response to hypoxia during which hTid-1S expression was down-regulated. We also found that overexpression of hTid-1S results in the inhibition of HSP27 phosphorylation, F-actin polymerization, and actin cytoskeleton organization in transduced HaCaT keratinocytes. This study further proposes that the loss of hTid-1S expression in the basal layer of skin epidermis correlates with the enhanced HSP27 phosphorylation, keratinocyte hyperproliferation, and excess actin cytoskeleton organization in lesional psoriatic skin.