Identification of pigment epithelium-derived factor as a direct target of the p53 family member genes

Sasaki, Yasushi; Naishiro, Yasuyoshi; Oshima, Yuichiro; Imai, Kohzoh; Nakamura, Yusuke; Tokino, Takashi

doi:10.1038/sj.onc.1208695

Cited by 46 publications

(44 citation statements)

References 37 publications

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“…Recent studies indicate that p63 proteins can bind DNA through response element (p63RE) slightly different to p53RE conferring responsiveness to p63 but not p53 proteins. 18,19 The DNp63 isoforms can bind DNA through p53RE and can exert dominant-negative effects over p53, p73 and p63 activities by either competing for DNA binding sites or by direct protein interaction (for a review Benard et al 20 ). DNp63 isoforms were also shown to directly activate specific gene targets not induced by TA isoforms.…”

Section: P63mentioning

confidence: 99%

“…Recent studies indicate that p73 proteins can bind DNA through response element slightly different to p53RE conferring responsiveness to p73 but not p53 proteins. 19 Biological activities of the p73 isoforms So far, there have been limited data concerning the expression patterns of individual p73 proteins, due to a lack of antibodies that distinguish between the different isoforms. The p73 gene is expressed in all normal tissues studied to date, although expression is at very low level.…”

Section: P63 and Cancermentioning

confidence: 99%

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p53/p63/p73 isoforms: an orchestra of isoforms to harmonise cell differentiation and response to stress

2006

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Abstractp63, p73 and p53 compose a family of transcription factors involved in cell response to stress and development. p53 is the most frequently mutated gene in cancer (50%) and loss of p53 activity is considered to be ubiquitous to all cancers. Recent publications may have a profound impact on our understanding of p53 tumour suppressor activity. p63, p73 and p53 genes have a dual gene structure conserved in drosophila, zebrafish and man. They encode for multiple p63, p73 or p53 proteins containing different protein domains (isoforms) due to multiple splicing, alternative promoter and alternative initiation of translation. In this review, we describe the different isoforms of p63, p73, p53 and their roles in development and cancer. The changes in the interactions between p53, p63 and p73 isoforms are likely to be fundamental to our understanding in the transition between normal cell cycling and the onset of tumour formation. Cell Death and Differentiation (2006) Introduction p53 was discovered in 1979 as a protein interacting with the oncogenic T antigen from SV40 virus. 1-5 p53 protein is the product of a pivotal tumor-suppressor gene whose inactivation by mutation or interaction with viral or overexpressed cellular proteins occurs in almost all cancers. 6 The p53 protein integrates multiple cellular stress signals assessing cellular damages to trigger either cell-cycle arrest or programmed cell death (apoptosis). 7 These effects are predominantly due to p53's ability to bind DNA through p53-responsive element (p53RE) 8,9 and regulate the transcription of genes involved in these processes, such as p21 10 (cell cycle arrest), Puma 11 or Scotin 12 (apoptosis). Thereby, p53 prevents proliferation of genetically abnormal cells and thus cancer formation.Two p53-related genes, p63 and p73, were identified in 1997. 13,14 The high level of sequence similarity between p63, p73 and p53 proteins, particularly in the DNA binding domain, allows p63 and p73 to transactivate p53-responsive genes causing cell cycle arrest and apoptosis. Therefore, p63, p73 and p53 genes form a family of transcription factor. However, they are not functionally entirely redundant and the primary role of each p53 family member -as determined by transgenetic knockout mice -illustrates that each protein has its own unique functions.We recently published that the p53 gene family has a dual gene structure conserved from drosophila to man. 15 Like most of the genes in the human genome, 16 p53 gene family members express multiple mRNA variants due to multiple splicing and alternative promoters. Hence, p53 gene family members express different forms of p53 protein containing different domain of the protein (isoforms). In this review, we will summarise the different isoforms of p63, p73 and p53 expressed in human, mouse and drosophila. p63The mouse p63 gene is composed of 15 exons spanning over 208 000 bp (GenBank Accession Number: AF533892) on chromosome 16, while the human p63 gene is composed of 15 exons, spanning over 270 000 bp on chromosome 3q2...

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Section: P63mentioning

confidence: 99%

Section: P63 and Cancermentioning

confidence: 99%

p53/p63/p73 isoforms: an orchestra of isoforms to harmonise cell differentiation and response to stress

2006

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“…These results demonstrate that p63 binds to the VDR promoter in vivo. Detailed analysis of the promoter region of p63 responsive genes has resulted in the identification of responsive elements that are specifically activated by p63 (Osada et al, 2005;Sasaki et al, 2005). The p63 responsive element appears to differ from the canonical (RRRCWWGYYY) responsive element of p53 in the CWWG core binding element as well as in the flanking RRR and YYY stretches (Osada et al, 2005).…”

Section: Identification Of Vitamin D Receptor As a Target Of P63mentioning

confidence: 99%

“…Next, we wanted to investigate whether upregulation of VDR by p63 results in differentiation in SaoS2 (osteosarcoma) cells (Sasaki et al, 2005). SaoS2 cells transiently transfected with p63g showed a significant increase in number of cells with elongated cytoplasmic processes and flattened fibroblastic appearance.…”

Section: Identification Of Vitamin D Receptor As a Target Of P63mentioning

confidence: 99%

Identification of vitamin D receptor as a target of p63

2006

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“…TAp63g has also been shown to activate the expression of Jagged 1 and Jagged 2, which are involved in Notch signaling, whereas Notch 1 activation has also been shown to suppress DNp63a expression, demonstrating a cross-talk between these pathways (7,8). Additional studies have shown that the biological effects of p63 in development and tumor suppression is exerted through the regulation of multiple signaling pathways (9)(10)(11)(12)(13)(14)(15)(16)(17). p73, another member of the p53 family, was also discovered based on structural similarities to p53 (18).…”

Section: Introductionmentioning

confidence: 99%

p63 Overexpression Induces the Expression of Sonic Hedgehog

Caserta

Kommagani²,

Yuan

et al. 2006

Molecular Cancer Research

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p63 and p73 are members of the p53 protein family and have been shown to play an important role in cell death, development, and tumorigenesis. In particular, p63 has been shown to be involved in the maintenance of epidermal stem cells and in the stratification of the epidermis. Sonic Hedgehog (Shh) is a morphogen that has also been implicated to play a role in epithelial stem cell proliferation and in the development of organs. Recently, Shh has also been shown to play an important role in the progression of a variety of cancers. In this report, we show that p63 and p73 but not p53 overexpression induces Shh expression. In particular, p63; and p63B (both TA and #N isoforms) and TAp73B isoform induce Shh. Expression of Shh was found to be significantly reduced in mouse embryo fibroblasts obtained from p63À/À mice. The naturally occurring p63 mutant TAp63;(R279H) and the tumor suppressor protein p14 ARF inhibited the TAp63;-mediated transactivation of Shh. The region À228 to À102 bp of Shh promoter was found to be responsive to TAp63;-induced transactivation and TAp63; binds to regions within the Shh promoter in vivo.

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Identification of pigment epithelium-derived factor as a direct target of the p53 family member genes

Cited by 46 publications

References 37 publications

p53/p63/p73 isoforms: an orchestra of isoforms to harmonise cell differentiation and response to stress

p53/p63/p73 isoforms: an orchestra of isoforms to harmonise cell differentiation and response to stress

Identification of vitamin D receptor as a target of p63

p63 Overexpression Induces the Expression of Sonic Hedgehog

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