Ratio disruption of the Δ133p53 and TAp53 isoform equilibrium correlates with poor clinical outcome in intrahepatic cholangiocarcinoma

Nutthasirikul, Nichapavee; Limpaiboon, Temduang; Leelayuwat, Chanvit; Patrakitkomjorn, Siriporn; Jearanaikoon, Patcharee

doi:10.3892/ijo.2013.1818

Cited by 46 publications

(44 citation statements)

References 19 publications

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“…Based on the observation that different p53 isoforms can be differentially expressed in tumors compared with normal tissue, an importance of alternative isoforms in carcinogenesis became clear [174,175,176]. For example, abnormal expression of p53 isoforms was reported in acute myeloid leukemia (AML), cholangiocarcinoma, colon carcinoma, glioblastoma, head and neck tumors, lung tumors, and ovarian tumors [177,178,179,180,181,182]. It was shown that normal breast tissue expresss p53α, p53β, and p53γ, whereas the expression of p53β and p53γ is lost in 60% of breast tumors, which instead frequently overexpress the isoform Δ133p53 [183].…”

Section: Inducible/modified Proteoforms Of P53mentioning

confidence: 99%

p53 Proteoforms and Intrinsic Disorder: An Illustration of the Protein Structure–Function Continuum Concept

Uversky

2016

IJMS

165

123

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Although it is one of the most studied proteins, p53 continues to be an enigma. This protein has numerous biological functions, possesses intrinsically disordered regions crucial for its functionality, can form both homo-tetramers and isoform-based hetero-tetramers, and is able to interact with many binding partners. It contains numerous posttranslational modifications, has several isoforms generated by alternative splicing, alternative promoter usage or alternative initiation of translation, and is commonly mutated in different cancers. Therefore, p53 serves as an important illustration of the protein structure–function continuum concept, where the generation of multiple proteoforms by various mechanisms defines the ability of this protein to have a multitude of structurally and functionally different states. Considering p53 in the light of a proteoform-based structure–function continuum represents a non-canonical and conceptually new contemplation of structure, regulation, and functionality of this important protein.

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Section: Inducible/modified Proteoforms Of P53mentioning

confidence: 99%

p53 Proteoforms and Intrinsic Disorder: An Illustration of the Protein Structure–Function Continuum Concept

Uversky

2016

IJMS

165

123

View full text Add to dashboard Cite

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“…In renal cell carcinoma (RCC), p53β and Δ133p53 isoforms are overexpressed in tumor cells compared with normal cells 77. Other studies have shown that p53 isoforms are also abnormally expressed in AML, cholangiocarcinoma, glioblastoma, head and neck tumors, colon carcinoma, and ovarian and lung tumors,78–83 and it can be expected that numerous other types of cancer are concerned.…”

Section: Role Of P53 Isoforms In Human Cancer and Other Pathologiesmentioning

confidence: 99%

“…Indeed, mutant p53 breast patients expressing p53γ have as good a prognosis as WT p53 breast cancer patients, while mutant p53 breast cancer patients not expressing p53γ have a particularly poor prognosis, and would benefit from additional treatment 75. In cholangiocarcinoma, Δ133p53 overexpression is associated with a shortened overall survival 83. In acute myeloid leukemia, determination of p53 isoform expression revealed distinct p53 protein biosignatures correlating with clinical outcome 81,99…”

Section: Overview Of the Clinical Implications Of P53 Isoform Activitmentioning

confidence: 99%

Uncovering the role of p53 splice variants in human malignancy: a clinical perspective

Surget¹,

Khoury²,

Bourdon³

2013

OTT

223

140

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Thirty-five years of research on p53 gave rise to more than 68,000 articles and reviews, but did not allow the uncovering of all the mysteries that this major tumor suppressor holds. How p53 handles the different signals to decide the appropriate cell fate in response to a stress and its implication in tumorigenesis and cancer progression remains unclear. Nevertheless, the uncovering of p53 isoforms has opened new perspectives in the cancer research field. Indeed, the human TP53 gene encodes not only one but at least twelve p53 protein isoforms, which are produced in normal tissues through alternative initiation of translation, usage of alternative promoters, and alternative splicing. In recent years, it became obvious that the different p53 isoforms play an important role in regulating cell fate in response to different stresses in normal cells by differentially regulating gene expression. In cancer cells, abnormal expression of p53 isoforms contributes actively to cancer formation and progression, regardless of TP53 mutation status. They can also be associated with response to treatment, depending on the cell context. The determination of p53 isoform expression and p53 mutation status helps to define different subtypes within a particular cancer type, which would have different responses to treatment. Thus, the understanding of the regulation of p53 isoform expression and their biological activities in relation to the cellular context would constitute an important step toward the improvement of the diagnostic, prognostic, and predictive values of p53 in cancer treatment. This review aims to summarize the involvement of p53 isoforms in cancer and to highlight novel potential therapeutic targets.

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“…Multiple studies have now shown that p53 isoforms have distinct functions and frequently contribute to diseases including cancer (4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18). Elevated expression of the D40p53 isoform has been associated with metastatic melanoma and triple-negative breast cancers (7,19).…”

Section: Introductionmentioning

confidence: 99%

A Study of TP53 RNA Splicing Illustrates Pitfalls of RNA-seq Methodology

et al. 2016

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TP53 undergoes multiple RNA-splicing events, resulting in at least nine mRNA transcripts encoding at least 12 functionally different protein isoforms. Antibodies specific to p53 protein isoforms have proven difficult to develop, thus researchers must rely on the transcript information to infer isoform abundance. In this study, we used deep RNA-seq, droplet digital PCR (ddPCR), and real-time quantitative reverse transcriptase PCR (RT-qPCR) from nine human cell lines and RNA-seq data available for tumors in The Cancer Genome Atlas to analyze TP53 splice variant expression. All three methods detected expression of the FL/40TP53a_T1 variant in most human tumors and cell lines. However, other less abundant variants were only detected with PCRbased methods. Using RNA-seq simulation analysis, we determined why RNA-seq is unable to detect less abundant TP53 transcripts and discuss the implications of these findings for the general interpretation of RNA-seq data. Cancer Res; 76(24); 7151-9. Ó2016 AACR.

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Ratio disruption of the Δ133p53 and TAp53 isoform equilibrium correlates with poor clinical outcome in intrahepatic cholangiocarcinoma

Cited by 46 publications

References 19 publications

p53 Proteoforms and Intrinsic Disorder: An Illustration of the Protein Structure–Function Continuum Concept

p53 Proteoforms and Intrinsic Disorder: An Illustration of the Protein Structure–Function Continuum Concept

Uncovering the role of p53 splice variants in human malignancy: a clinical perspective

A Study of TP53 RNA Splicing Illustrates Pitfalls of RNA-seq Methodology

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