Structural organization of cornified cell envelopes and alterations in inherited skin disorders

Ishida‐Yamamoto, Akemi; Iizuka, Hajime

doi:10.1111/j.1600-0625.1998.tb00295.x

Cited by 107 publications

(73 citation statements)

References 133 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Cornified envelopes, the functional end point of keratinocyte terminal differentiation, form a rigid and protective protein barrier in the outer layers of the epidermis (for a recent review see Ref. 37). Envoplakin is a component of both desmosomes and cornified envelopes (13) and is thus a potentially important structural protein of the epidermis.…”

Section: Discussionmentioning

confidence: 99%

Structure and Regulation of the Envoplakin Gene

Määttå¹,

Ruhrberg²,

Watt

2000

Journal of Biological Chemistry

View full text Add to dashboard Cite

Envoplakin, a member of the plakin family of proteins, is a component of desmosomes and the epidermal cornified envelope. To understand how envoplakin expression is regulated, we have analyzed the structure of the mouse envoplakin gene and characterized the promoters of both the human and mouse genes. The mouse gene consists of 22 exons and maps to chromosome 11E1, syntenic to the location of the human gene on 17q25. The exon-intron structure of the mouse envoplakin gene is common to all members of the plakin family: the Nterminal protein domain is encoded by 21 small exons, and the central rod domain and the C-terminal globular domain are coded by a single large exon. The C terminus shows the highest sequence conservation between mouse and human envoplakins and between envoplakin and the other family members. The N terminus is also conserved, with sequence homology extending to Drosophila Kakapo. A region between nucleotides ؊101 and 288 was necessary for promoter activity in transiently transfected primary keratinocytes. This region is highly conserved between the human and mouse genes and contains at least two different positively acting elements identified by site-directed mutagenesis and electrophoretic mobility shift assays. Mutation of a GC box binding Sp1 and Sp3 proteins or a combined E box and Krü ppel-like element interacting with unidentified nuclear proteins virtually abolished promoter activity. 600 base pairs of the mouse upstream sequence was sufficient to drive expression of a ␤-galactosidase reporter gene in the suprabasal layers of epidermis, esophagus, and forestomach of transgenic mice. Thus, we have identified a regulatory region in the envoplakin gene that can account for the expression pattern of the endogenous protein in stratified squamous epithelia.

show abstract

Section: Discussionmentioning

confidence: 99%

Structure and Regulation of the Envoplakin Gene

Määttå¹,

Ruhrberg²,

Watt

2000

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…Loricrin, involucrin, the small proline-rich proteins (SPR's), and other substrates are crosslinked by transglutaminase, while the intermediate filament network is reorganized into compact macrofibrils oriented parallel to the body surface. 2 Filaggrin is a highly charged, cationic protein that aids aggregation and subsequent disulfide bonding of keratin filaments. 3 It is derived from profilaggrin, a large (4400 kD), phosphorylated precursor expressed as keratohyalin granules in the granular layer of the epidermis.…”

Section: Introductionmentioning

confidence: 99%

Inducible expression of filaggrin increases keratinocyte susceptibility to apoptotic cell death

et al. 2000

View full text Add to dashboard Cite

Filaggrin is an intermediate filament associated protein that aids the packing of keratin filaments during terminal differentiation of keratinocytes. Premature aggregation of keratin filaments is prevented by filaggrin expression as the inactive precursor, profilaggrin, which is localized in keratohyalin granules in vivo. We have previously shown that filaggrin constructs, when transiently transfected into epithelial cells, lead to a collapsed keratin cytoskeletal network and dysmorphic nuclei with features of apoptosis. The apparent transfection rate is low with filaggrin constructs, supporting their disruptive role but hindering further study. To bypass this problem, we generated stable keratinocyte cell lines that express mature human filaggrin using a tetracyclineinducible promoter system. We found that cell lines expressing filaggrin, but not control cell lines, exhibited increased sensitivity to multiple apoptotic stimuli as measured by morphologic and biochemical criteria. None of the cell lines showed an increase in endogenous expression of filaggrin in response to the same stimuli. Filaggrin expression alone was insufficient to induce apoptosis in these keratinocyte cell lines. We conclude that filaggrin, due to its keratin binding ability, primes cells for apoptosis. Because filaggrin is expressed at a level of the epidermis where keratinocytes are in transition between the nucleated granular and the anucleate cornified layers, we hypothesize that filaggrin aids in the terminal differentiation process by facilitating apoptotic machinery. Cell Death and Differentiation (2000) 7, 566 ± 573.

show abstract

“…They then undergo terminal differentiation, which is characterized by the production of a highly insoluble rigid structure termed cornified cell envelope (CE) 1 beneath the plasma membrane (1)(2)(3). Transglutaminase enzymes catalyze the assembly of this structure via formation of ⑀-(␥-glutamyl)lysine bonds between envelope precursors.…”

mentioning

confidence: 99%

Expression of Human Cystatin A by Keratinocytes Is Positively Regulated via the Ras/MEKK1/MKK7/JNK Signal Transduction Pathway but Negatively Regulated via the Ras/Raf-1/MEK1/ERK Pathway

Takahashi¹,

Honma²,

Ishida‐Yamamoto³

et al. 2001

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

Cystatin A, a cysteine proteinase inhibitor, is a cornified cell envelope constituent expressed in the upper epidermis. We previously reported that a potent protein kinase C activator, 12-O-tetradecanoylphorbol-13-acetate, increases human cystatin A expression by the activation of AP-1 proteins. Here, we delineate the signaling cascade responsible for this regulation. Co-transfection of the cystatin A promoter into normal human keratinocytes together with a dominant active form of ras increased the promoter activity by 3-fold. In contrast, a dominant negative form of ras suppressed basal cystatin A promoter activity. Further analyses disclosed that transfection of dominant negative forms of raf-1, MEK1, ERK1, ERK2, or wild-type MEKK1 all increased cystatin A promoter activity in normal human keratinocytes, whereas wild-type raf-1, ERK1, ERK2, or dominant negative forms of MEKK1, MKK7, or JNK1 suppressed the promoter activity. The increased or decreased promoter activity reflected the expression of cystatin A on mRNA and protein levels. These effects were not observed when a cystatin A promoter with a T2 (؊272 to ؊278) deletion was used. In contrast, transfection of dominant negative forms of MKK3, MKK4, or p38 did not affect cystatin A promoter activity. Immunohistochemical analyses revealed that phosphorylated active extracellular signal-regulated kinases and c-Jun N-terminal kinase were expressed in the nuclei of basal cells and cells in the suprabasal-granular cell layer, respectively. These results indicate that the expression of cystatin A is regulated via mitogen-activated protein kinase pathways positively by Ras/MEKK1/MKK7/JNK and negatively by Ras/Raf/MEK1/ERK.

show abstract

Structural organization of cornified cell envelopes and alterations in inherited skin disorders

Cited by 107 publications

References 133 publications

Structure and Regulation of the Envoplakin Gene

Structure and Regulation of the Envoplakin Gene

Inducible expression of filaggrin increases keratinocyte susceptibility to apoptotic cell death

Expression of Human Cystatin A by Keratinocytes Is Positively Regulated via the Ras/MEKK1/MKK7/JNK Signal Transduction Pathway but Negatively Regulated via the Ras/Raf-1/MEK1/ERK Pathway

Contact Info

Product

Resources

About