Cloning and chromosomal mapping of the human p53-related KET gene to Chromosome 3q27 and its murine homolog Ket to mouse Chromosome 16

Augustin, Martin; Bamberger, Casimir; Paul, Dieter; Schmale, Hartwig

doi:10.1007/s003359900891

Cited by 57 publications

(39 citation statements)

References 24 publications

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“…Among them, a pivotal role in tumor suppression is played by the recently established p53 family. It consists of a group of proteins, whose oldest and the most studied member, p53, was identified more than 20 years ago (Lane and Crawford, 1979;Linzer and Levine, 1979;Oren and Levine, 1983;Beinz et al, 1984), whereas its homologs p73 and p63 and their related and truncated spliced forms have been characterized in the last few years (Kaghad et al, 1997;Schmale, 1997;Osada et al, 1998;Senoo et al, 1998;Augustin et al, 1998;Trink et al, 1998;Yang et al, 1999). The basic modular structure of p53 family members comprises a N-terminal transcriptional activation domain, a central DNA-binding domain and a C terminus with oligomeric and regulatory activities (McKinney and Prives, 2005).…”

Section: Introductionmentioning

confidence: 99%

Mutant p53: an oncogenic transcription factor

Strano¹,

Dell’Orso²,

Agostino³

et al. 2007

Oncogene

243

184

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Inactivation of tumor-suppressor genes is one of the key hallmarks of a tumor. Unlike other tumor-suppressor genes, p53 is inactivated by missense mutations in half of all human cancers. It has become increasingly clear that the resulting mutant p53 proteins do not represent only the mere loss of wild-type p53 tumor suppressor activity, but gain new oncogenic properties favoring the insurgence, the maintenance, the spreading and the chemoresistance of malignant tumors. The actual challenge is the fine deciphering of the molecular mechanisms underlying the gain of function of mutant p53 proteins. In this review, we will focus mainly on the transcriptional activity of mutant p53 proteins as one of the potential molecular mechanisms. To date, the related knowledge is still quite scarce and many of the raised questions of this review are yet unanswered.

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Section: Introductionmentioning

confidence: 99%

Mutant p53: an oncogenic transcription factor

Strano¹,

Dell’Orso²,

Agostino³

et al. 2007

Oncogene

243

184

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“…[1][2][3][4] The revelation of an internal promoter within this family was first attributed to TP63. 4 TP63 has a domain topology similar to TP53, with an N-terminal transactivation domain, a central sequence-specific DNA-binding domain, and a C-terminal oligomerization domain.…”

mentioning

confidence: 99%

Distinct Expression Profiles of p63 Variants during Urothelial Development and Bladder Cancer Progression

Karni-Schmidt

Castillo-Martín

HuaiShen

et al. 2011

The American Journal of Pathology

120

112

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The TP63 gene, a member of the TP53 tumor suppressor gene family, can be expressed as at least six isoforms due to alternative promoter use and alternative splicing. The lack of p63 isoform-specific antibodies has limited the analysis of the biological significance of p63. We report a novel set of well-defined antibodies to examine p63 isoforms in mouse and human urothelium during embryogenesis and tumor progression, respectively. We provide evidence that basal and intermediate urothelial cells express p63 isoforms, with the TAp63 variant the first to be detected during development, whereas umbrella cells are characterized by a p63-negative phenotype. Notably, we report that p63-null mice develop a bladder with an abnormal urothelium, constituted by a single layer of cells that express uroplakin II and low molecular weight cytokeratins, consistent with an umbrella cell phenotype. Finally, analysis of 202 human bladder carcinomas revealed a new categorization of invasive tumors into basal-like (positive for ⌬Np63 and high molecular weight cytokeratins and negative for low molecular weight cytokeratins) versus luminal-like (negative for ⌬Np63 and high molecular weight cytokeratins and positive for low molecular weight cytokeratins) phenotypes, with ⌬Np63 expression associated with an aggressive clinical course and poor prognosis. This study highlights the relevance of p63 isoforms in both urothelial development and bladder carcinoma progression, with ⌬Np63 acting as an oncogene in certain invasive bladder tumors.

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“…Recently, p63 and p73, two p53 homologues, were identified (2,27,39,54,57). These proteins exhibit a high sequence and structural homology to the p53 protein.…”

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confidence: 99%

The ΔNp63α Phosphoprotein Binds the p21 and 14-3-3σ Promoters In Vivo and Has Transcriptional Repressor Activity That Is Reduced by Hay-Wells Syndrome-Derived Mutations

Westfall

Mays

Sniezek

et al. 2003

Molecular and Cellular Biology

317

390

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p63 is a recently identified homolog of p53 that is found in the basal layer of several stratified epithelial tissues such as the epidermis, oral mucosa, prostate, and urogenital tract. Studies with p63 ؊/؊ mice and analysis of several human autosomal-dominant disorders with germ line p63 mutations suggest p63 involvement in maintaining epidermal stem cell populations. The p63 gene encodes six splice variants with reported transactivating or dominant-negative activities. The goals of the current study were to determine the splice variants that are expressed in primary human epidermal keratinocytes (HEKs) and the biochemical activity p63 has in these epithelial cell populations. We found that the predominant splice variant expressed in HEKs was ⌬Np63␣, and it was present as a phosphorylated protein. During HEK differentiation, ⌬Np63␣ and p53 levels decreased, while expression of p53 target genes p21 and 14-3-3 increased. ⌬Np63␣ had transcriptional repressor activity in vitro, and this activity was reduced in ⌬Np63␣ proteins containing point mutations, corresponding to those found in patients with Hay-Wells syndrome. Further, we show that ⌬Np63␣ and p53 can bind the p21 and 14-3-3 promoters in vitro and in vivo, with decreased binding of p63 to these promoters during HEK differentiation. These data suggest that ⌬Np63␣ acts as a transcriptional repressor at select growth regulatory gene promoters in HEKs, and this repression likely plays an important role in the proliferative capacity of basal keratinocytes.

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Cloning and chromosomal mapping of the human p53-related KET gene to Chromosome 3q27 and its murine homolog Ket to mouse Chromosome 16

Cited by 57 publications

References 24 publications

Mutant p53: an oncogenic transcription factor

Mutant p53: an oncogenic transcription factor

Distinct Expression Profiles of p63 Variants during Urothelial Development and Bladder Cancer Progression

The ΔNp63α Phosphoprotein Binds the p21 and 14-3-3σ Promoters In Vivo and Has Transcriptional Repressor Activity That Is Reduced by Hay-Wells Syndrome-Derived Mutations

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