Filaggrin: A Keratin Filament Associated Protein<sup>a</sup>

Dale, Beverly A.; Resing, Katheryn A.; Lonsdale‐Eccles, John D.

doi:10.1111/j.1749-6632.1985.tb50420.x

Cited by 152 publications

(75 citation statements)

References 29 publications

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“…Progress has also been made in understanding the regulation of genes expressed in human keratinocytes (21,22) and in elucidating their structure (17,18) and function (14). Other participants involved in keratin filament assembly and cornified envelope formation have also been identified (5,8,9). Future experiments can be expected to describe in ever increasing detail the function of these proteins in the differentiating keratinocyte.…”

Section: Discussionmentioning

confidence: 99%

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Molecular biology of keratinocyte differentiation.

Eckert

Rorke

1989

Environ Health Perspect

140

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Epidermal keratinocytes (skin cells) are highly specialized epithelial cells designed to perform a very specific function, separation of the organism from its environment. lb accomplish this the cells synthesize precursors and assemble them into two distinct structures, the cornified envelope and keratin intermediate filaments.The intermediate filaments are assembled from keratin monomers and the cornified envelope is assembled from a protein called involucrin and several other proteins. Expression of involucrin and the keratins genes are regulated as a function of the stage of keratinocyte differentiation and by various external agents such as calcium and vitamin A. lo study the function of these structures and the regulation of precursor production we have cloned cDNA and genomic clones encoding involucrin and four of the keratin polypeptides.Retinoids profoundly alter the differentiation pattern of human epidermal keratinocytes, but the underlying biochemical basis of this change is not known. In this report we describe retinoid-promoted changes in keratin gene expression that may, in part, be responsible for the alteration in cellular phenotype in the presence of the vitamin. We also describe the novel structure of the human 40 kD keratin, a member of the keratin family that is retinoid responsive and is likely to be important during epidermal development. Finally, we describe the structure of the envelope precursor protein, involucrin, as determined from its DNA sequence and speculate on its role in cornified envelope formation.

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Section: Discussionmentioning

confidence: 99%

“…1). During this process keratinocytes ini-tiate synthesis of important differentiation-dependent structural and catalytic proteins including involucrin (2,3), the keratins (4), filaggrin (5), and transglutaminase (6). In addition, they go through marked morphological and cytostructural changes (1,7).…”

Section: Introductionmentioning

confidence: 99%

Molecular biology of keratinocyte differentiation.

Eckert

Rorke

1989

Environ Health Perspect

140

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“…Loss-of-function mutations in the filaggrin gene (FLG) were found to be associated with AD in independent populations (Irvine 2007). FLG protein is present in the granular layers of the epidermis, and the keratohyalin granules in the granular layers are predominantly composed of the 400-kDa polyprotein, profilaggrin (Dale et al 1985;Listwan and Rothnagel 2004;Candi et al 2005). On the differentiation of keratinocytes, profilaggrin is dephosphorylated and cleaved into 10-12 essentially identical 37-kDa filaggrin peptides.…”

Section: Introductionmentioning

confidence: 99%

Filaggrin null mutations are associated with atopic dermatitis and elevated levels of IgE in the Japanese population: a family and case–control study

et al. 2008

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Filaggrin (FLG) plays an important role in the barrier function of the skin. Several loss-of-function mutations in the FLG gene have been identified in patients with ichthyosis vulgaris, and these null mutations are associated with atopic dermatitis (AD) development. In this study, we examined tag single nucleotide polymorphisms (tSNPs) and null mutations in FLG for possible associations with AD and atopic phenotypes in a Japanese population. Transmission disequilibrium test of 105 AD families showed that the null allele of the S2554X variant of FLG tended to be overtransmitted to AD-affected offspring; however, the P value did not reach statistical significance. In a casecontrol comparison of 376 AD cases and 923 nonallergic controls, the null allele of S2554X was significantly associated with AD (P = 0.0012), and the association was strengthened in subjects with AD alone (P = 0.000024). We found that 3321delA and S2554X were also associated with elevated levels of immunoglobulin E (IgE). Combined null mutation carriers were observed more in AD patients and in subjects with high IgE than in control subjects. The combined P value for the family and case-control data was significant for the S2554X and combined null mutations. Our data further support the importance of FLG in AD development.

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“…One of the most quantitatively significant IF-IFAP systems is the interaction of filaggrin with epidermal keratin IF (1,(4)(5)(6)(7). These proteins are expressed in terminally differentiating epidermis and constitute the "keratin" of mammalian epidermis as a filament-interfilamentous matrix.…”

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confidence: 99%