Transcription factor AP2 and its role in epidermal-specific gene expression.

Leask, Andrew; Byrne, Carolyn; Fuchs, Elaine

doi:10.1073/pnas.88.18.7948

Cited by 222 publications

(156 citation statements)

References 27 publications

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“…1 Instead of CAAT or TATA boxes, the promoter region of the GALC gene demonstrated to have signal sequences susceptible to the transcription factors SP1 (5 0 -CCCGCC-3 0 ), YY1 (5 0 -AAA TGG-3 0 ) and AP2 (5 0 -GCCTGCAGGC-3 0 ). 1,14,17,18 Even though several groups were working on slightly different promoter regions, these findings were similar. 1,4,5,14 One approach to explain the decreased transcription of the GALC gene is to hypothesize that inhibiting transcription factors bind to an appropriate promoter region leading to decreased GALC transcription.…”

Section: Repression Of the Galc Gene Galc Promoter Region And Transcrmentioning

confidence: 63%

Implications of galactocerebrosidase and galactosylcerebroside metabolism in cancer cells

Beier

Görögh

2005

Intl Journal of Cancer

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Galactosylcerebroside is known to be overexpressed upon the cellular surface of a variety of cancers. In squamous cell carcinomas of the head and neck, one explanation for galactosylcerebroside accumulation has been identified as a transcriptional repression of the galactocerebrosidase gene. Galactocerebrosidase is the enzyme responsible for degrading galactosylcerebroside to ceramide. Ceramide is an important apoptosis activator, whereas galactosylcerebroside functions as an inhibitor. A shift of the ceramide metabolism balance in favor of glycosylated forms has been identified as a mechanism of drug resistance for several antineoplastic agents. Our review elaborates on possible explanations for galactocerebrosidase suppression and on other explanations for increased glycosphingolipid concentration within cancer cell membranes. Furthermore, conjecturable influences of a repressed galactocerebrosidase expression on tumor biology are to be explained. The inhibiting transcription factors YY1 and AP2 have been identified as potential galactocerebrosidase gene suppressors. The resulting accumulation of galactosylcerebroside promotes a reduction of cellular adhesion and inhibits apoptosis, leading to increased cellular growth, migration and prolonged cell survival contributing to carcinogenesis. ' 2005 Wiley-Liss, Inc.

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Section: Repression Of the Galc Gene Galc Promoter Region And Transcrmentioning

confidence: 63%

Implications of galactocerebrosidase and galactosylcerebroside metabolism in cancer cells

Beier

Görögh

2005

Intl Journal of Cancer

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“…Finally, both promoter FP3 and intronic enhancer FPC sequences bind AP-2 with equivalent a nity and speci®city, suggesting that they are coregulated in vivo. Thus, juxtaposition of both enhancer and promoter, as in the natural context or in the reporter constructs described (Bates and Hurst, The conserved sequence 5'-CTGCAGG-3' in both FP3 and FPC, which represents the core binding sequence identi®ed by methylation protection experiments in FP3 (Hollywood and Hurst, 1993), is also found in elements of E-cadherin and keratin gene promoters, reported to function through AP-2 factors (Hennig et al, 1996;Leask et al, 1991). However, we failed to observe competition to either FP3 or FPC by an E-cadherin`E-pal' oligonucleotide (data not shown).…”

Section: Discussionmentioning

confidence: 96%

AP-2 transcription factors in the regulation of ERBB2 gene transcription by oestrogen

et al. 2000

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Transcription of the ERBB2 oncogene is repressed by oestrogen in human breast cancer cells. We show that a 218 bp fragment of the human ERBB2 gene promoter is responsive to oestrogen in transient transfection in ZR75.1 and SKBR.3 cells when the oestrogen receptor is expressed. Deletion analysis of this fragment shows that a sequence located at the 5' end, which is known to mediate ERBB2 overexpression in breast cancer, is also responsible for the oestrogen response. This sequence binds AP-2 transcription factors and appears functionally identical to an element of the oestrogen-dependent enhancer described in the ®rst intron of human ERBB2. We observed that oestrogen treatment down-regulates expression of AP-2 proteins but does not a ect the DNA binding activity of AP-2. Constitutive expression of AP2b or AP-2g, but not AP-2a, abrogates the estrogenic repression. Our results demonstrate that AP-2 transcription factors are implicated in the oestrogenic regulation of ERBB2 gene expression and suggest a complex interplay involving the di erent AP-2 isoforms and other unidenti®ed factors. Oncogene (2000) 19, 280 ± 288.

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“…AP-1 (Casatorres et al, 1994), AP2, and Sp1/Sp3 (Byrne and Fuchs, 1993;Kaufman et al, 2002) act on the keratin 5 promoter. The promoter regions of keratin 14 were targets of AP2 (Leask et al, 1991;Sinha et al, 2000), AP-1, Ets (Sinha et al, 2000), CACCC-Box binding protein, SP1 (Sinha and Fuchs, 2001), and Skn-1a (Sugihara et al, 2001). AP-1 and AP2 were also involved as the transcription factors in the early epidermal development of Xenopus (Luo et al, 2002;Peng et al, 2002).…”

Section: Discussionmentioning

confidence: 99%

Metamorphosis‐dependent transcriptional regulation of xak‐c, a novel Xenopus type I keratin gene

Watanabe

Tanaka

Kobayashi

et al. 2002

Developmental Dynamics

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Anuran larvae transform their epidermis to the adult counterpart during metamorphosis. The major event of this process is the proliferation of larval epidermal basal cells and their differentiation into adult ones. The present study isolated novel type I keratin cDNA dubbed xak-c (Xenopus adult keratin-c) that was exclusively expressed in adult epidermal basal cells. The gene started its expression in the larval epidermis at the onset of metamorphosis. Thyroid hormone (TH) induced the precocious expression of the gene in the epidermis of premetamorphic tadpoles. To study the transcriptional regulation of this gene in relation to epidermal metamorphosis, a 2.8 kb 5 -flanking region of xak-c was cloned and its promoter activity was investigated. Gene constructs were made so as to contain the xak-c promoter region and gene of EGFP or luciferase as a reporter gene and were transfected into various types of cells, which revealed that the 5 -flanking region had an epidermal cellspecific transcriptional activity in both anurans and mammals. Larval skin tissues of Xenopus were transfected with the constructs and cultured in the presence and absence of TH, which showed that the promoter region is responsive to TH, although the region did not contain the consensus TH response element-like sequence. In sharp contrast, the promoter region did not respond to TH in the adult skin, clearly indicating that the cloned region contains specific sequences that respond to metamorphosis-dependent transcription factor(s).

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Transcription factor AP2 and its role in epidermal-specific gene expression.

Abstract: The epidermis is a stratified squamous epithelium whose maijor differention-specific products are kera-

Cited by 222 publications

References 27 publications

Implications of galactocerebrosidase and galactosylcerebroside metabolism in cancer cells

Implications of galactocerebrosidase and galactosylcerebroside metabolism in cancer cells

AP-2 transcription factors in the regulation of ERBB2 gene transcription by oestrogen

Metamorphosis‐dependent transcriptional regulation of xak‐c, a novel Xenopus type I keratin gene

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