Related calcium-binding proteins map to the same subregion of chromosome 1q and to an extended region of synteny on mouse chromosome 3

Dorin, Julia R.; Emslie, Elisabeth; Heyningen, Veronica van

doi:10.1016/0888-7543(90)90027-r

Cited by 56 publications

(32 citation statements)

References 27 publications

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“…This region has been of interest in recent cytogenetic studies on breast cancer because of the frequent loss of heterozygosity or deletions in chromosome 1 (q21-qter) (23)(24)(25)(26). Also, SlOa and calpain have been mapped but not localized to chromosome 1 (41,42).…”

Section: Tigsklqda--g-lenqk-p -Qyirk-gad -Nllkasstl Eglkklmgnl Densdqmentioning

confidence: 99%

Down-regulation of a member of the S100 gene family in mammary carcinoma cells and reexpression by azadeoxycytidine treatment.

Lee

Tomasetto

Swisshelm

et al. 1992

Proc. Natl. Acad. Sci. U.S.A.

146

116

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A cDNA clone, designated CaN19 (originally called clone 19), isolated by subtractive hybridization, contains sequences that are preferentially expressed in normal mammary epithelial cells but not in breast tumor cells. Comparison of its deduced amino acid sequence with sequences in the GenBank data base revealed similarity with the S100 protein family, a group of small Ca(2+)-binding modulator proteins involved in cell cycle progression and cell differentiation. CaN19 expression is down-regulated in normal cells by A23187, a calcium ionophore, suggesting that its regulation is calcium-dependent. We have assigned CaN19 to human chromosome 1q21-q24, a region containing four other S100-related genes. In contrast to CaN19 mRNA expression, most members of the S100 protein family are activated or overexpressed in tumor cells. Synchronization experiments by growth-factor deprivation demonstrated a biphasic induction of CaN19 expression in normal cells, approximately 2-fold in early G1 phase and another 2- to 3-fold at the G1/S boundary. Exposure of mammary tumor cells to 5-aza-2'-deoxycytidine, an inhibitor of DNA methylation, reactivated the expression of CaN19 mRNA.

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Section: Tigsklqda--g-lenqk-p -Qyirk-gad -Nllkasstl Eglkklmgnl Densdqmentioning

confidence: 99%

Down-regulation of a member of the S100 gene family in mammary carcinoma cells and reexpression by azadeoxycytidine treatment.

Lee

Tomasetto

Swisshelm

et al. 1992

Proc. Natl. Acad. Sci. U.S.A.

146

116

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“…Indications that S100 genes might form a gene cluster came from their colocalization on human chromosome 1 (12,(14)(15)(16). The S100 gene cluster described in this work contains at least six different S100 genes, including two previously unreported members of this family.…”

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confidence: 99%

Six S100 genes are clustered on human chromosome 1q21: identification of two genes coding for the two previously unreported calcium-binding proteins S100D and S100E.

Engelkamp

Schäfer

Matteï

et al. 1993

Proc. Natl. Acad. Sci. U.S.A.

166

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The human genome contains large regions that are highly structured. Sequence-related members ofmultigene families are often found in a dustered organization. Here we describe a previously unrecognized gene cluster composed ofgenes coding for calcium-binding proteins ofthe S100 family. The linkage of six S100 genes was established by pulsed-field gel electrophoresis, and a contiguous DNA sequence of 15 kilobases containing the full coding region of four different S100 genes was characterized. This is the tightest mammalian gene cluster discovered so far to our knowledge. Two additional S100 genes are located within the cluster, both of which exhibit unique structural features when compared with other S100 genes. The product of S100E is cysteine-rich, whereas that of SIOOD contains a long hydrophobic N-terminal tail. The gene cluster was assigned to chromosome 1q21, one of the bands showing rearrangements in neoplasms at high frequency. The deregulated expression of some S100 genes in the cluster during tumor progression suggests that chromosomal abnormalities may influence the expression of S100 genes in late stages of cancer, particularly in association with the formation of metastases.

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“…Interestingly, however, several small calcium-binding proteins have also been mapped at 1q21 (12,21) and some of them, like calcyclin, have been shown to be expressed in the epidermis (66). At the same time, the genes for another two epidermal-specific intermediate filament-associated proteins, involucrin (14) and loricrin (67), have been mapped to 1q21.…”

Section: Resultsmentioning

confidence: 99%

“…Recently, we isolated and partially characterized the human gene and confirmed that it encodes a polyprotein consisting of many tandemly arranged filaggrin repeats (18,41). We showed that it is highly polymorphic, both with respect to the numbers of repeats (10, 11, or 12 repeats within the human population) and to the actual sequences themselves (neighboring repeats show as much as 20% sequence variation). We also identified sequences on the amino and carboxyl termini that are unlike the filaggrin repeats; however, their functions remain obscure.…”

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confidence: 99%

Profilaggrin is a major epidermal calcium-binding protein.

Markova¹,

Marekov²,

Chipev³

et al. 1993

Mol. Cell. Biol.

126

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Profilaggrin is a major highly phosphorylated protein component of the keratohyalin granules of mammalian epidermis. It contains 10 to 12 tandemly repeated filaggrin units and is processed into the intermediate filament-associated protein filaggrin by specific dephosphorylation and proteolysis during terminal differentiation of the epidermal cells. Later, filaggrin itself is degraded to free amino acids that participate in maintenance of epidermal flexibility. The present paper describes the structural organization of the 5' region of the human profilaggrin gene as well as the amino terminus of the profilaggrin protein. profilaggrin mRNA, are transcribed from the profilaggrin gene system at earlier stages of epidermal differentiation. The amino terminus of profilaggrin exhibits a significant homology to the small calcium-binding S100-like proteins. It contains two a-helical regions, termed EF-hands, that bind calcium in vitro. This is the first example of functional calcium-binding domains fused to a structural protein. We suggest that in addition to its role in filament aggregation and the maintenance of epidermal flexibility, profilaggrin may play an important role in the differentiation of the epidermis by autoregulating its own processing in a calciumdependent manner or by participating in the transduction of calcium signal in epidermal cells.Terminal differentiation of human epidermis involves the expression of sets of novel structural proteins including the keratin intermediate filaments (composed of keratins 1 and 10) and two other proteins, loricrin and profilaggrin, which are codeposited as keratohyalin granules (7,60). Loricrin is now known to be a principal component of the insoluble cell envelope to which it is covalently cross-linked both by disulfide bonds and by N-(y-glutamyl)lysine cross-links formed by the action of epidermal transglutaminases (24, 25). Profilaggrin has a completely different fate. This protein initially accumulates as an insoluble phosphorylated polyprotein precursor consisting largely of filaggrin repeats (36,44,55). It has a half-life of about 6 h, and at very late stages of differentiation, it is dephosphorylated and proteolytically processed into individual filaggrin molecules (22, 45, 51) that presumably interact with and align the keratin filaments in a plane parallel to the surface of the epidermis (8, 57, 58). Filaggrin itself has a half-life of only about 24 h in stratum corneum cells (45) and is degraded mostly into free amino acids that are required for maintenance of epidermal osmolarity and hence flexibility and perhaps even for immunological protection of the organism (9,43,56). Thus, on the basis of our current understanding, the product of the profilaggrin gene is ultimately utilized in at least two important functions in normal epidermis. This series of events is clearly abnormal in a number of diseases of cornification in the epidermis, particularly the various classes of ichthyoses (65). For example, in epidermolytic hyperkeratosis and lamellar ich-* Correspo...

show abstract

Related calcium-binding proteins map to the same subregion of chromosome 1q and to an extended region of synteny on mouse chromosome 3

Cited by 56 publications

References 27 publications

Down-regulation of a member of the S100 gene family in mammary carcinoma cells and reexpression by azadeoxycytidine treatment.

Down-regulation of a member of the S100 gene family in mammary carcinoma cells and reexpression by azadeoxycytidine treatment.

Six S100 genes are clustered on human chromosome 1q21: identification of two genes coding for the two previously unreported calcium-binding proteins S100D and S100E.

Profilaggrin is a major epidermal calcium-binding protein.

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