Functions of NIPP1 in keratinocyte biology and cutaneous wound repair.

The skin forms a protective barrier over the body. The outer skin layer or epidermis mainly consists of keratinocytes that originate from stem cells in the basal layer or the hair shaft bulge. Keratinocytes gradually move up to the surface of the skin, a process that is accompanied by a step-wise differentiation and eventually apoptosis. When damaged, the skin shows a remarkable ability to heal. An important step of the wound healing process involves the migration of keratinocytes to the wound edge, and their subsequent proliferation and differentiation until the wound bed is completely re-epithelialized. We have found that the nuclear scaffold protein NIPP1 is essential for the migration, proliferation and differentiation of epithelial cells and regulates the expression of genes that are important for cutaneous wound healing. With the current research project we want to delineate the exact role of NIPP1 in skin homeostasis and wound healing, using keratinocyte and skin-specific NIPP1 knockout models. Since all known functions of NIPP1 are mediated by associated protein Ser/Thr phosphatase-1 (PP1), we also want to examine whether recently developed highly specific and cell-permeable effectors of PP1 interfere with keratinocyte biology and epidermal wound healing.