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

作者：Choi Ji Hye; Choi Dae Kyoung; Sohn Kyung Cheol; Kwak Sang Su; Suk Jinkyu; Lim Jong Soon; Shin Incheol; Kim Sung Woo; Lee Jeung Hoon; Joe Cheol O^*

来源：Journal of Biological Chemistry, 2012, 287(31): 25954-25963.

DOI：10.1074/jbc.M111.313809

The biochemical mechanism by which the human tumorous imaginal disc1(S) (hTid-1(S)) interferes with actin cytoskeleton organization in keratinocytes of human skin epidermis was investigated. We found that hTid-1, specifically hTid-1(S), 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-1(S) 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-1(S) expression was supported by the inhibition of HSP27 phosphorylation and MK5 activity in HeLa cells in response to hypoxia during which hTid-1(S) expression was down-regulated. We also found that overexpression of hTid-1(S) 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-1(S) 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.

• 出版日期2012-7-27