The Expression of p63 during Epidermal Remodeling in Psoriasis

Shen, Chun-Shen; Tsuda, Tatsuya; Fushiki, Shinji; Mizutani, Hitoshi; Yamanishi, Kiyofumi

doi:10.1111/j.1346-8138.2005.tb00755.x

Cited by 25 publications

(27 citation statements)

References 23 publications

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“…The normal Ki-67 and p63 protein expression in the lesional skin of our patient is consistent with previous observations showing that the p63 protein is expressed in the skin despite the presence of a mutation [27][28][29]. Molecular alterations probably result in reduced transcriptional activity of the impaired p63 on several gene promoters [30][31][32][33][34][35].…”

supporting

confidence: 78%

Ectrodactyly-ectodermal dysplasia-clefting syndrome with unusual cutaneous vitiligoid and psoriasiform lesions due to a novel single point TP63 gene mutation

Wawrzycki¹,

Pietrzak²,

Chodorowska³

et al. 2019

pdia

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supporting

confidence: 78%

Ectrodactyly-ectodermal dysplasia-clefting syndrome with unusual cutaneous vitiligoid and psoriasiform lesions due to a novel single point TP63 gene mutation

Wawrzycki¹,

Pietrzak²,

Chodorowska³

et al. 2019

pdia

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“…This result suggests the possibility that p63 suppresses differentiation via KGF receptor expression while inducing differentiation via the JNK/AP-1 pathway. Furthermore, p63 dysregulation is also observed in psoriasis, a common skin disease marked by the hyperproliferation and delayed differentiation of epidermal cells (39). p63 is expressed throughout almost the whole epidermis, except for a few layers located at or near the skin surface.…”

Section: Discussionmentioning

confidence: 99%

p63/p51-induced Onset of Keratinocyte Differentiation via the c-Jun N-terminal Kinase Pathway Is Counteracted by Keratinocyte Growth Factor

Ogawa

Okuyama

Egawa

et al. 2008

Journal of Biological Chemistry

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p63/p51, a homolog of the tumor suppressor protein p53, is chiefly expressed in epithelial tissues, including the epidermis. p63 affects cell death similar to p53, and also plays important roles in the development of epithelial tissues and the maintenance of epithelial stem cells. Because it remains unclear how p63 regulates epithelial cell differentiation, we examined the function(s) of p63 in keratinocyte differentiation through the use of a keratinocyte culture system. ⌬Np63␣ (⌬Np51B), a p63 isoform specifically expressed in basal keratinocytes, suppressed the differentiation of specific late-stage proteins, such as filaggrin and loricrin. In contrast, ⌬Np63␣ induced keratin 1 (K1), which is expressed at the start of differentiation, via c-Jun N-terminal kinase (JNK)/AP-1 activation. However, p63 did not induce K1 expression in the basal layer in vivo, although basal keratinocytes had high levels of p63. This discrepancy was explained by the suppression of K1 expression by dermis-secreted keratinocyte growth factor. This suppression occurred via extracellular signal-related kinase (ERK) signaling, and counteracted the p63-mediated induction of K1. Thus, a precise balance between p63 and keratinocyte growth factor mediates the onset of epithelial cell differentiation, through JNK and ERK signaling. These data may provide mechanistic explanations for the pathological features of skin diseases, including psoriasis.p63, also known as p51, is a homologue of the tumor suppressor protein p53. The p53 family of transcription factors consists of three members, p53, p63, and p73 (1). The p63 gene possesses two transcriptional start sites that generate transcripts encoding proteins with (termed TAp63) or without (termed ⌬Np63) an N-terminal transactivation (TA) 3 domain. In addition, alternative splicing primarily results in 3 isoforms, p63␣, p63␤, and p63␥, each of which is unique at its C terminus. Despite a high similarity in their structures, members of the p53 family seem to play mostly distinct functions in tumor suppression and development. Whereas mutations of p53 are found in more than half of all human cancers, the overexpression of p63, and particularly of the ⌬Np63␣ isoform, has been reported in a variety of squamous cell cancers (2-4). Furthermore, p63 mutations result in various human hereditary diseases involving ectodermal dysplasia, a variety of abnormalities characterized by defects in the skin and its associated structures (5). p63 Ϫ/Ϫ mice also display severe abnormalities of the skin, limbs, and mammary glands (6, 7). This is in contrast to p53 Ϫ/Ϫ mice that develop apparently normal (8). The skin of p63 Ϫ/Ϫ mice has an epidermis that is thin, lacks stratification, and does not express markers of keratinocyte differentiation. These features indicate a critical role for p63 in regulating various facets of epithelial cell biology.The epidermis is organized in several distinct overlying layers designated, from the bottom to the surface, as the basal, spinous, granular, and cornified layers (9, 10). Act...

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“…Psoriasis is also characterized by altered p63 staining in interfollicular skin. 37 Evaluation of c-Jun and JunB conditional KOs for p63 expression and juns staining in p63 KOs could shed light as to the fine tuning regulation of p63.…”

Section: Discussionmentioning

confidence: 99%

Identification of New p63 Targets in Human Keratinocytes

Testoni¹,

Borrelli²,

Tenedini³

et al. 2006

Cell Cycle

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ABSTRACTp63 is a transcription factor involved in the development of ectodermal tissues, including limb, skin and, in general, multilayered epithelia. We identified both activated and repressed genes in human keratinocytes via gene expression profiling of p63-depleted cells and validated 21 new primary targets by RT-PCR and ChIP location analysis. The p63 isoforms differentially activate or repress selected promoters. ChIPs in primary keratinocytes indicate that p63 targets are generally shared with p53, but some are p63-specific. Several growth suppressors are among repressed genes. The newly identified genes belong to pathways of growth and differentiation and are regulated in HaCaT differentiation and in stratification of human skin.

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The Expression of p63 during Epidermal Remodeling in Psoriasis

Cited by 25 publications

References 23 publications

Ectrodactyly-ectodermal dysplasia-clefting syndrome with unusual cutaneous vitiligoid and psoriasiform lesions due to a novel single point TP63 gene mutation

Ectrodactyly-ectodermal dysplasia-clefting syndrome with unusual cutaneous vitiligoid and psoriasiform lesions due to a novel single point TP63 gene mutation

p63/p51-induced Onset of Keratinocyte Differentiation via the c-Jun N-terminal Kinase Pathway Is Counteracted by Keratinocyte Growth Factor

Identification of New p63 Targets in Human Keratinocytes

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