The International Journal of Biochemistry & Cell Biology
Molecules in focusPsoriasin (S100A7)
Introduction
Psoriasin is a relatively new member of the S100 gene family that was first identified by[9]as a 11.4 kDa protein induced in squamous epithelial cells of the epidermis isolated from skin involved by psoriasis. Psoriasin shares homology and chromosomal proximity with other members of the S100 gene family, justifying classification as S100A7. The S100 genes encode small cytoplasmic and secreted proteins that share EF-hand helix-loop-helix domains that are important for their function as calcium binding proteins[14]. Broad roles have been proposed for these genes in cell growth, differentiation and determination of cell shape.
Section snippets
Structure
The Psoriasin gene maps to chromosome 1q21.2-q22, within a region that encompasses at least 12 of the S100 gene family (see Fig. 1) and several other epidermal differentiation genes1, 13. Although the gene has not been sequenced it is likely that it conforms to the organization of adjacent S100 genes. In most cases, these possess a simple three exon/two intron structure, with the first exon contributing most of the 5′ untranslated region to the mRNA and the second and third exons covering the
Biological function
Psoriasin expression is restricted to keratinocytes and breast epithelial cells, in contrast to the overlapping pattern of the related subgroup of S100 genes A8, A9 and A12, which are also expressed in hematopoietic cells of myeloid lineage. It is known to be both a cytoplasmic and secreted protein that is upregulated in keratinocytes in response to calcium and retinoic acid and during abnormal pathways of differentiation in culture, where Psoriasin is amongst the most highly induced proteins[5]
Role in pathology
The monogram Psoriasin endorses its association with psoriasis and high levels of expression in psoriasiform epidermal hyperplasia adjacent to traumatic skin ulcers have also been observed. However, the gene is clearly also expressed under conditions of abnormal epithelial differentiation and is secreted by neoplastic keratinocytes in carcinoma of the bladder[2]. More recently, Psoriasin and the related S100 A8 and A9 proteins have also been found in other abnormal epithelia, including
Role in breast cancer
Disruption of calcium signalling pathways has been implicated as a central mechanism in tumorigenesis and specifically in the process of invasion and metastasis[7]. One important component of the intracellular calcium signalling system is the S100 family of genes, which are known to be frequently expressed in breast cancer cell lines and tissues[12], but with often intriguingly different patterns of regulation that illustrate the cell type and stage-specific regulation of expression that is
In the future
It is now important to identify the receptor and/or cellular targets of a protein that is so highly expressed under certain conditions and stages of epithelial differention, in order to understand its biological function in inflammatory skin disease as well as in neoplasia. Such knowledge might on the one hand become useful in the development of new strategies to block the local epidermal inflammatory response that characterizes psoriasis, and on the other hand for the application of a clinical
Acknowledgements
This work was supported by grants from the Canadian Breast Cancer Research Initiative (CBCRI) and the U.S. Army Medical Research and Material Command (USAMRMC).
References (15)
- et al.
Bladder squamous cell carcinomas express psoriasin and externalise it to the urine
J. Urol.
(1996) - et al.
Characterisation of a new calcium binding protein abundant in amniotic fluid, CAAF2, which is produced by fetal epidermal keratinocytes during embryogenesis
Biochem. Biophys. Res. Commun.
(1996) - et al.
Psoriasin: a novel chemotactic protein
J. Invest. Dermatol.
(1996) - et al.
Molecular cloning, occurrence, and expression of a novel partially secreted protein “psoriasin” that is highly upregulated in psoriatic skin
J. Invest. Dermatol.
(1991) - et al.
Isolation of a YAC clone covering a cluster of nine S100 genes on human chromosome 1q21: rationale for a new nomenclature of the S100 calcium binding protein family
Genomics
(1995) - et al.
The S100 family of EF-hand calcium binding proteins: functions and pathology
Trends Biochem.
(1996) - et al.
Macrophage-stimulating protein induces proliferation and migration of murine keratinocytes
Exp. Cell Res.
(1996)
Cited by (97)
Effects of frequent teat stimulation on antimicrobial component production in mammary glands of lactating goats
2022, Veterinary Immunology and ImmunopathologyExpression profile of drosomycin-like defensin in oral epithelium and oral carcinoma cell lines
2013, Archives of Oral BiologyCitation Excerpt :The expression of β-defensin-2 and -3 is upregulated by certain types of cytokines and bacteria.14,15 Some of these antimicrobial peptides may function as proto- or suppressor-oncogenes.7,16,17 Psoriasin and β-defensin-1 may be proto- and suppressor-oncogenes, respectively.18–22
Role of innate host defense proteins in oral cancerogenesis
2024, Periodontology 2000The identification, regulation and functional study of the differentially expressed genes in human esophageal squamous cell carcinoma
2023, New Research On Esophageal Cancer: Horizons In Cancer ResearchCopy number variation of bovine S100A7 as a positional candidate affected body measurements
2023, Animal Biotechnology