MS100a7a15

Last updated

The S100 calcium-binding protein mS100a7a15 is the murine ortholog of human S100A7 (Psoriasin) and human S100A15 (Koebnerisin). mS100a7a15 is also known as S100a15, mS100a7 and mS100a7a and is encoded by the mS100a7a gene (alias: S100a15) [1] [2]

Contents

S100 proteins are a diverse calcium-binding family that mediate fundamental cellular and extracellular processes including cell proliferation and differentiation, cell migration, and the antimicrobial host defense as antimicrobial peptides.

mS100a7a15 was first cloned as mS100a15 from adult mouse skin (FVB/N mice, clone RP1-128L15, accession no.: AL591704). [2] Today, the protein is of further interest because of its role in innate immunity, epidermal cell maturation and epithelial tumorigenesis. Additionally, it can serve as surrogate model to study hS100A7 and hS100A15 functions.

Function

Epithelial homeostasis and antimicrobial host defence

Skin: In new-born mouse skin, mS100a7a15 is localized to the epidermal granular and cornified layers of the interfollicular epidermis and to the maturing cells of hair follicles. [2] [3] In maturing keratinocytes, mS100a7a15 is induced by calcium mediated differentiation dependent on protein kinase C (PKC). [2] It is upregulated in a TLR4 dependent manner by E.coli stimulation and might have antimicrobial effects against E.coli like its human counterparts. [4] In the dermis, it is expressed by the smooth muscle cells of the panniculus carnosus. [2]

Breast: mS100a7a15 is weakly expressed in normal mammary gland tissue. [3]

Epithelial Carcinogenesis

Breast cancer: mS100a7a15 is upregulated in DMBA induced mammary gland tumors confined to epithelial tumor cells. [3] mS100a7a15 overexpression in mammary epithelial cells enhances proliferation, angiogenesis and metastasis through induction of prometastatic and angiogenic factors like CCL2, Cox-2, MMP2, MMP9 and VEGF. Furthermore mS100a7a15 recruits tumor-associated-macrophages (TAM) through RAGE and Stat3 activation to promote tumorigenesis. [5] [6]

Inflammation

mS100a7a15 is upregulated in inflamed skin. [3] TPA (12-O-Tetradecanoylphorbol-13-acetate), a potent PKC activator, induces mS100a7a15 expression. TPA induces mS100a7a15 through AP-1 but not NF-κB. [2] Similar to psoriasin, mS100a7a15 recruits leukocytes and induces proinflammatory chemokines as well as cytokines in keratinocytes through RAGE activation as an alarmin. [5] [7] Similar to its human counterparts, mS100a7a15 mediates inflammation through RAGE (like psoriasin) and through an unknown receptor (like koebnerisin). [7] A bi-transgenic mouse model (K5-tTA/TetOmS100a7a15) that expresses abundant mS100a7a15 throughout the basal epidermal layer showed an increased infiltration of CD3+ and CD4+ T lymphocytes into the skin that was associated with an increased production of Th1 and Th17 cytokines and cathelicidin/LL-37. [7]

Special characteristics

Genomic organization and mRNA splice variants

mS100a7a15 is encoded within the murine equivalent of the human EDC on chromosome 3qF1. The mouse transcript is organized in three exons and two introns, spanning an open reading frame of 327 nucleotides. [2]

Protein

The deduced mS100a7a15 protein sequence has two helix-loop-helix motifs corresponding to the for S100 proteins typical conserved C-terminal and a variant N-terminal EF-hand calcium binding sites. The translated mS100a7a15 protein features 109 amino acids, with a calculated molecular weight of 12.87 kDa and a predicted pI of 6.18. [2]

Evolution

The mS100a7a15 gene is encoded in a single genomic region on chromosome 3qF1 that corresponds to the human chromosome 1q21 where psoriasin (S100A7) and koebnerisin (S100A15) are encoded. This indicates that the mS100a7a15 gene is close to the ancestor of the human orthologs. [2] [8]

Related Research Articles

<span class="mw-page-title-main">Keratinocyte</span> Primary type of cell found in the epidermis

Keratinocytes are the primary type of cell found in the epidermis, the outermost layer of the skin. In humans, they constitute 90% of epidermal skin cells. Basal cells in the basal layer of the skin are sometimes referred to as basal keratinocytes. Keratinocytes form a barrier against environmental damage by heat, UV radiation, water loss, pathogenic bacteria, fungi, parasites, and viruses. A number of structural proteins, enzymes, lipids, and antimicrobial peptides contribute to maintain the important barrier function of the skin. Keratinocytes differentiate from epidermal stem cells in the lower part of the epidermis and migrate towards the surface, finally becoming corneocytes and eventually be shed off, which happens every 40 to 56 days in humans.

Mouse mammary tumor virus (MMTV) is a milk-transmitted retrovirus like the HTL viruses, HI viruses, and BLV. It belongs to the genus Betaretrovirus. MMTV was formerly known as Bittner virus, and previously the "milk factor", referring to the extra-chromosomal vertical transmission of murine breast cancer by adoptive nursing, demonstrated in 1936, by John Joseph Bittner while working at the Jackson Laboratory in Bar Harbor, Maine. Bittner established the theory that a cancerous agent, or "milk factor", could be transmitted by cancerous mothers to young mice from a virus in their mother's milk. The majority of mammary tumors in mice are caused by mouse mammary tumor virus.

<span class="mw-page-title-main">Amphiregulin</span> Protein-coding gene in the species Homo sapiens

Amphiregulin, also known as AREG, is a protein synthesized as a transmembrane glycoprotein with 252 aminoacids and it is encoded by the AREG gene. in humans.

<span class="mw-page-title-main">S100 protein</span> Family of vertebrate proteins involved in cell division and inflammation

The S100 proteins are a family of low molecular-weight proteins found in vertebrates characterized by two calcium-binding sites that have helix-loop-helix ("EF-hand-type") conformation. At least 21 different S100 proteins are known. They are encoded by a family of genes whose symbols use the S100 prefix, for example, S100A1, S100A2, S100A3. They are also considered as damage-associated molecular pattern molecules (DAMPs), and knockdown of aryl hydrocarbon receptor downregulates the expression of S100 proteins in THP-1 cells.

<span class="mw-page-title-main">Protein S100-A4</span>

Protein S100-A4 (S100A4) is a protein that in humans is encoded by the S100A4 gene.

<span class="mw-page-title-main">Proto-oncogene Wnt-1</span>

Proto-oncogene Wnt-1, or Proto-oncogene Int-1 homolog is a protein that in humans is encoded by the WNT1 gene.

<span class="mw-page-title-main">S100A7</span>

S100 calcium-binding protein A7 (S100A7), also known as psoriasin, is a protein that in humans is encoded by the S100A7 gene.

<span class="mw-page-title-main">S100A8</span> Protein-coding gene in Homo sapiens

S100 calcium-binding protein A8 (S100A8) is a protein that in humans is encoded by the S100A8 gene. It is also known as calgranulin A.

<span class="mw-page-title-main">S100A9</span>

S100 calcium-binding protein A9 (S100A9) also known as migration inhibitory factor-related protein 14 (MRP14) or calgranulin B is a protein that in humans is encoded by the S100A9 gene.

<span class="mw-page-title-main">S100A11</span>

S100 calcium-binding protein A11 (S100A11) is a protein that in humans is encoded by the S100A11 gene.

<span class="mw-page-title-main">Teratocarcinoma-derived growth factor 1</span>

Teratocarcinoma-derived growth factor 1 is a protein that in humans is encoded by the TDGF1 gene. The protein is an extracellular, membrane-bound signaling protein that plays an essential role in embryonic development and tumor growth. Mutations in this gene are associated with forebrain defects. Pseudogenes of this gene are found on chromosomes 2, 3, 6, 8, 19 and X. Alternate splicing results in multiple transcript variants.

<span class="mw-page-title-main">FGF10</span> Protein-coding gene in the species Homo sapiens

Fibroblast growth factor 10 is a protein that in humans is encoded by the FGF10 gene.

<span class="mw-page-title-main">HOXA5</span> Protein-coding gene in humans

Homeobox protein Hox-A5 is a protein that in humans is encoded by the HOXA5 gene.

<span class="mw-page-title-main">SERPINB13</span> Gene of the species Homo sapiens

Serpin B13 is a protein that in humans is encoded by the SERPINB13 gene.

<span class="mw-page-title-main">ALOXE3</span> Protein-coding gene in the species Homo sapiens

Epidermis-type lipoxygenase 3 is a member of the lipoxygenase family of enzymes; in humans, it is encoded by the ALOXE3 gene. This gene is located on chromosome 17 at position 13.1 where it forms a cluster with two other lipoxygenases, ALOX12B and ALOX15B. Among the human lipoxygenases, ALOXE3 is most closely related in amino acid sequence to ALOX12B. ALOXE3, ALOX12B, and ALOX15B are often classified as epidermal lipoxygenases, in distinction to the other three human lipoxygenases, because they were initially defined as being highly or even exclusively expressed and functioning in skin. The epidermis-type lipoxygenases are now regarded as a distinct subclass within the multigene family of mammalian lipoxygenases with mouse Aloxe3 being the ortholog to human ALOXE3, mouse Alox12b being the ortholog to human ALOX12B, and mouse Alox8 being the ortholog to human ALOX15B [supplied by OMIM]. ALOX12B and ALOXE3 in humans, Alox12b and Aloxe3 in mice, and comparable orthologs in other in other species are proposed to act sequentially in a multistep metabolic pathway that forms products that are structurally critical for creating and maintaining the skin's water barrier function.

<span class="mw-page-title-main">S100A15</span>

S100 calcium-binding protein A15 (S100A15), also known as koebnerisin and S100 calcium-binding protein A7A (S100A7A), is a protein that in humans is encoded by the S100A7A (alias:S100A15) gene.

<span class="mw-page-title-main">S100A14</span> Protein-coding gene in the species Homo sapiens

S100 calcium binding protein A14 (S100A14) is a protein that in humans is encoded by the S100A14 gene.

<span class="mw-page-title-main">Forkhead box d1</span> Human protein-coding gene

Forkhead box D1 is a protein that in humans is encoded by the FOXD1 gene. Forkhead d1 is a kidney expressed transcription factor maps at the chromosome 5 at position 5q12—q13, identified in Drosophila forkhead protein and mammalian HNF3 transcription factor. The name of was derived from two spiked head structures in the embryos of Drosophila forkhead mutant. It belong to transcription factor family that displays remarkable functional diversity and involved in a wide variety of biological processes. The most commonly used synonyms for Forkhead D1 are, FOX D1, FREAC-4 and BF2.

The epidermal differentiation complex (EDC) is a gene complex comprising over fifty genes encoding proteins involved in the terminal differentiation and cornification of keratinocytes, the primary cell type of the epidermis. In humans, the complex is located on a 1.9 Mbp stretch within chromosome 1q21. The proteins encoded by EDC genes are closely related in terms of function, and evolutionarily they belong to three distinct gene families: the cornified envelope precursor family, the S100 protein family and the S100 fused type protein (SFTP) family.

Chromosome 1 open reading frame 68, or C1orf68, is a human gene which encodes for skin-specific protein 32. C1orf68 gene is expressed in the skin, is apart of the epidermal differentiation complex, and potentially plays a role in epidermal cornification, and epidermal barrier function.

References

  1. ↑ "Entrez Gene: S100 calcium binding protein A7A".
  2. 1 2 3 4 5 6 7 8 9 Wolf, R; Voscopoulos, CJ; FitzGerald, PC; Goldsmith, P; Cataisson, C; Gunsior, M; Walz, M; Ruzicka, T; Yuspa, SH (July 2006). "The mouse S100A15 ortholog parallels genomic organization, structure, gene expression, and protein-processing pattern of the human S100A7/A15 subfamily during epidermal maturation". The Journal of Investigative Dermatology. 126 (7): 1600–8. doi: 10.1038/sj.jid.5700210 . PMID   16528363.
  3. 1 2 3 4 Webb, M; Emberley, ED; Lizardo, M; Alowami, S; Qing, G; Alfia'ar, A; Snell-Curtis, LJ; Niu, Y; Civetta, A; Myal, Y; Shiu, R; Murphy, LC; Watson, PH (17 February 2005). "Expression analysis of the mouse S100A7/psoriasin gene in skin inflammation and mammary tumorigenesis". BMC Cancer. 5: 17. doi:10.1186/1471-2407-5-17. PMC   553966 . PMID   15717926.
  4. ↑ Büchau, AS; Hassan, M; Kukova, G; Lewerenz, V; Kellermann, S; Würthner, JU; Wolf, R; Walz, M; Gallo, RL; Ruzicka, T (November 2007). "S100A15, an antimicrobial protein of the skin: regulation by E. coli through Toll-like receptor 4". The Journal of Investigative Dermatology. 127 (11): 2596–604. doi: 10.1038/sj.jid.5700946 . PMID   17625598.
  5. 1 2 Nasser, MW; Qamri, Z; Deol, YS; Ravi, J; Powell, CA; Trikha, P; Schwendener, RA; Bai, XF; Shilo, K; Zou, X; Leone, G; Wolf, R; Yuspa, SH; Ganju, RK (1 February 2012). "S100A7 enhances mammary tumorigenesis through upregulation of inflammatory pathways". Cancer Research. 72 (3): 604–15. doi:10.1158/0008-5472.CAN-11-0669. PMC   3271140 . PMID   22158945.
  6. ↑ Shubbar, E; Vegfors, J; Carlström, M; Petersson, S; Enerbäck, C (July 2012). "Psoriasin (S100A7) increases the expression of ROS and VEGF and acts through RAGE to promote endothelial cell proliferation". Breast Cancer Research and Treatment (Submitted manuscript). 134 (1): 71–80. doi:10.1007/s10549-011-1920-5. PMID   22189627. S2CID   16289559.
  7. 1 2 3 Wolf, R; Mascia, F; Dharamsi, A; Howard, OM; Cataisson, C; Bliskovski, V; Winston, J; Feigenbaum, L; Lichti, U; Ruzicka, T; Chavakis, T; Yuspa, SH (8 December 2010). "Gene from a psoriasis susceptibility locus primes the skin for inflammation". Science Translational Medicine. 2 (61): 61ra90. doi:10.1126/scitranslmed.3001108. PMC   6334290 . PMID   21148126.
  8. ↑ Kulski, JK; Lim, CP; Dunn, DS; Bellgard, M (April 2003). "Genomic and phylogenetic analysis of the S100A7 (Psoriasin) gene duplications within the region of the S100 gene cluster on human chromosome 1q21". Journal of Molecular Evolution. 56 (4): 397–406. Bibcode:2003JMolE..56..397K. doi:10.1007/s00239-002-2410-5. PMID   12664160. S2CID   39365917.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.