Alternative splicing of p53 and p73: the novel p53 splice variant p53δ is an independent prognostic marker in ovarian cancer

Hofstetter, Gerda; Berger, Astrid; Fiegl, Heidi; Slade, Neda; Zorić, Arijana; Holzer, Barbara; Schuster, Eva; Möbus, V.; Reimer, Daniel; Daxenbichler, G.; Marth, Christian; Zeimet, Alain G.; Concin, Nicole; Zeillinger, Robert

doi:10.1038/onc.2009.482

Cited by 74 publications

(66 citation statements)

References 32 publications

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“…Alteration of p53 splice variants can also be induced by the insertion or deletion of nucleotides in TP53, especially if these occur in the introns or at exon splice junctions [49,50]. In ovarian cancer, p53 splice variants with C-terminal truncations frequently occur, and these have been shown to be associated with a poorer prognosis and enhanced chemoresistance [50]. Some p53 mutations result in an oncogenic gain of function (GOF) protein [51].…”

Section: The Importance Of Cadherins In Actin Cytoskeleton Remodelingmentioning

confidence: 99%

p53 regulates cytoskeleton remodeling to suppress tumor progression

Araki

Ebata

Guo

et al. 2015

Cell. Mol. Life Sci.

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Cancer cells possess unique characteristics such as invasiveness, the ability to undergo epithelial-mesenchymal transition, and an inherent stemness. Cell morphology is altered during these processes and this is highly dependent on actin cytoskeleton remodeling. Regulation of the actin cytoskeleton is, therefore, important for determination of cell fate. Mutations within the TP53 (tumor suppressor p53) gene leading to loss or gain of function (GOF) of the protein are often observed in aggressive cancer cells. Here, we highlight the roles of p53 and its GOF mutants in cancer cell invasion from the perspective of the actin cytoskeleton; in particular its reorganization and regulation by cell adhesion molecules such as integrins and cadherins. We emphasize the multiple functions of p53 in the regulation of actin cytoskeleton remodeling in response to the extracellular microenvironment, and oncogene activation. Such an approach provides a new perspective in the consideration of novel targets for anti-cancer therapy.

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Section: The Importance Of Cadherins In Actin Cytoskeleton Remodelingmentioning

confidence: 99%

p53 regulates cytoskeleton remodeling to suppress tumor progression

Araki

Ebata

Guo

et al. 2015

Cell. Mol. Life Sci.

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“…AS is known to impact protein usage by altering signals for phosphorylation, glycosylation, and trafficking (Hiller et al 2005). Recent research in mammalian species is drawing attention to the fact that AS and its regulatory pathways can have important physiological consequences for an organism, including the areas of cancer progression and immune repertoire generation (Hofstetter et al 2010;Sahoo and Im 2010).…”

Section: Introductionmentioning

confidence: 99%

Alternative splicing in teleost fish genomes: same-species and cross-species analysis and comparisons

et al. 2010

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Alternative splicing (AS) is a mechanism by which the coding diversity of the genome can be greatly increased. Rates of AS are known to vary according to the complexity of eukaryotic species potentially explaining the tremendous phenotypic diversity among species with similar numbers of coding genes. Little is known, however, about the nature or rate of AS in teleost fish. Here, we report the characteristics of AS in teleost fish and classification and frequency of five canonical AS types. We conducted both same-species and cross-species analysis utilizing the Genome Mapping and Alignment Program (GMAP) and an AS pipeline (ASpipe) to study AS in four genome-enabled species (Danio rerio, Oryzias latipes, Gasterosteus aculeatus, and Takifugu rubripes) and one species lacking a complete genome sequence, Ictalurus punctatus. AS frequency was lowest in the highly duplicated genome of zebrafish (17% of mapped genes). The compact genome of the pufferfish showed the highest occurrence of AS (approximately 43% of mapped genes). An inverse correlation between AS frequency and genome size was consistent across all analyzed species. Cross-species comparisons utilizing zebrafish as the reference genome allowed the identification of additional putative AS genes not revealed by zebrafish transcripts. Approximately, 50% of AS genes identified by same-species comparisons were shared among two or more species. A searchable website, the Teleost Alternative Splicing Database, was created to allow easy identification and visualization of AS transcripts in the studied teleost genomes. Our results and associated database should further our understanding of alternative splicing as an important functional and evolutionary mechanism in the genomes of teleost fish.

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“…15,23,[59][60][61][62][63][64] Fujita and colleagues determined that Δ133p53α inhibits senescence while p53β promotes senescence in normal human fibroblasts. They analyzed the expression of Δ133p53α and p53β in a cohort of colon adenomas and carcinomas and reported an association of the senescent phenotype of colon adenoma with reduced Δ133p53α and increased p53β expression.…”

Section: P53 Isoforms and Cancermentioning

confidence: 99%

p53 Isoforms: An Intracellular Microprocessor?

Khoury¹,

Bourdon²

2011

Genes & Cancer

147

125

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Normal function of the p53 pathway is ubiquitously lost in cancers either through mutation or inactivating interaction with viral or cellular proteins. However, it is difficult in clinical studies to link p53 mutation status to cancer treatment and clinical outcome, suggesting that the p53 pathway is not fully understood. We have recently reported that the human p53 gene expresses not only 1 but 12 different p53 proteins (isoforms) due to alternative splicing, alternative initiation of translation, and alternative promoter usage. p53 isoform proteins thus contain distinct protein domains. They are expressed in normal human tissues but are abnormally expressed in a wide range of cancer types. We have recently reported that p53 isoform expression is associated with breast cancer prognosis, suggesting that they play a role in carcinogenesis. Indeed, the cellular response to damages can be switched from cell cycle arrest to apoptosis by only manipulating p53 isoform expression. This may provide an explanation to the hitherto inconsistent relationship between p53 mutation, treatment response, and outcome in breast cancer. However, the molecular mechanism is still unknown. Recent reports suggest that it involves modulation of gene expression in a p53-dependent and -independent manner. In this review, we summarize our current knowledge about the biological activities of p53 isoforms and propose a molecular mechanism conciliating our current knowledge on p53 and integrating p63 and p73 isoforms in the p53 pathway.

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Alternative splicing of p53 and p73: the novel p53 splice variant p53δ is an independent prognostic marker in ovarian cancer

Cited by 74 publications

References 32 publications

p53 regulates cytoskeleton remodeling to suppress tumor progression

p53 regulates cytoskeleton remodeling to suppress tumor progression

Alternative splicing in teleost fish genomes: same-species and cross-species analysis and comparisons

p53 Isoforms: An Intracellular Microprocessor?

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