S100A7 (Psoriasin) Interacts with Epidermal Fatty Acid Binding Protein and Localizes in Focal Adhesion-Like Structures in Cultured Keratinocytes

Abstract

S100 proteins are calcium-responsive signaling proteins that are overexpressed in cancer and inflammatory diseases. They act by forming complexes with target proteins to modify target protein function. Identifying S100 intracellular distribution, site of action, and protein targets are important goals. S100A7 (psoriasin) is an important member of this family that is markedly overexpressed in psoriatic keratinocytes; however, its role in disease progression is poorly understood. In this study, we express S100A7 in normal keratinocytes as a means to study S100A7 function. We show that S100A7 is present in the cytosol and in BiP/GRP78-positive (endoplasmic reticulum) tubular structures. When cells are challenged with elevated intracellular calcium, cytoplasmic S100A7 redistributes to alpha-actinin- and paxillin-positive peripheral structures that contact the substrate surface. Epidermal fatty acid binding protein is also overexpressed in psoriasis, and is a putative target of S100A7 in keratinocytes. To study this interaction, we coexpressed S100A7 and epidermal fatty acid binding protein. These studies indicate that S100A7 and epidermal fatty acid binding protein colocalize in the cytoplasm in untreated cultures, and localize in peripheral structures in response to calcium challenge. In addition, S100A7 expression appears to stabilize epidermal fatty acid binding protein level, and vice versa. Moreover, the proteins can be coprecipitated in the presence of bifunctional cross-linker, suggesting that they are part of a common complex. The colocalization with alpha-actinin and paxillin suggests that S100A7 and epidermal fatty acid binding protein colocalize in focal adhesion-like structures following calcium treatment.

Differential expression and in vivo secretion of the antimicrobial peptides psoriasin (S100A7), RNase 7, human beta‐defensin‐2 and ‐3 in healthy human skin

“…Highest psoriasin expression was seen in differentiated cellular layers, which is in line with absent psoriasin expression in undifferentiated keratinocytes (19) and undifferentiated tumour cells of basal cell carcinoma (20). The distribution of RNase 7, hBD-2 and -3 is in concordance with their proposed function as a chemical shield against pathogens, as the first contact with microorganisms occurs in the stratum corneum (1,2).…”

Use of a Combination of Approaches to Identify and Validate Relevant Tumor-Associated Antigens and Their Corresponding Autoantibodies in Ovarian Cancer Patients

“…The other spot was identified as S100A7, which is a 11-kDa protein expressed by a wide variety of cells and is involved in the regulation of cell cycle progression and differentiation (21,22). The S100A7 protein is overexpressed in many cancers, such as breast, skin, bladder, and gastric cancer (23 -26).…”

Structural and functional analysis of fatty acid-binding proteins

“…KFABP has been shown to form a divalent cationdependent complex with S100A7, a calcium-regulated signaling protein (21). In cultured keratinocytes, coexpression of S100A7 and KFABP resulted in the protein-protein complex relocating from the cytoplasm to peripheral adhesionlike structures upon addition of calcium (21).…”

“…In cultured keratinocytes, coexpression of S100A7 and KFABP resulted in the protein-protein complex relocating from the cytoplasm to peripheral adhesionlike structures upon addition of calcium (21). The functional significance of these observations and the structural basis for the KFABP-S100A7 interaction are unknown.…”