ΔNp73: Misunderstood protein?

Irwin, Meredith S.

doi:10.4161/cbt.5.7.3023

Cited by 7 publications

(7 citation statements)

References 19 publications

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“…Functional studies of TAp73 and ΔNp73 have revealed differential effects in response to genotoxic stress [16,44-46]. TAp73 induces arrest and apoptosis, while in most systems ΔNp73 counteracts these pathways in response to ionizing radiation and genotoxic agents in vitro [as reviewed in [47]]. In other cell types, ΔNp73 induces apoptosis instead, underscoring the complexity of p73 isoform function.…”

Section: Discussionmentioning

confidence: 99%

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Overexpressed TP73 induces apoptosis in medulloblastoma

et al. 2007

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Background: Medulloblastoma is the most common malignant brain tumor of childhood. Children who relapse usually die of their disease, which reflects resistance to radiation and/or chemotherapy. Improvements in outcome require a better understanding of the molecular basis of medulloblastoma growth and treatment response. TP73 is a member of the TP53 tumor suppressor gene family that has been found to be overexpressed in a variety of tumors and mediates apoptotic responses to genotoxic stress. In this study, we assessed expression of TP73 RNA species in patient tumor specimens and in medulloblastoma cell lines, and manipulated expression of full-length TAp73 and amino-terminal truncated ΔNp73 to assess their effects on growth.

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Section: Discussionmentioning

confidence: 99%

“…The initial depiction of ΔNp73 and TAp73 as either anti- or pro-apoptotic appears oversimplified [as reviewed in [47]]. In fact, various chemotherapeutic agents can induce ΔNp73 expression in neoplastic cell lines, suggesting a role in apoptotic response [52,53].…”

Section: Discussionmentioning

confidence: 99%

Overexpressed TP73 induces apoptosis in medulloblastoma

et al. 2007

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“…The TA variants possess a transactivation domain while the DN variant is lacking the TA domain. Additionally, isoforms can undergo C-terminal splicing [79,80]. Although p53 is commonly mutated in human tumors this has not been demonstrably the case for either p63 or p73.…”

Section: The P53 Transcriptional Network and The Cell Death Responsementioning

confidence: 97%

“…Full-length p63 and p73 exhibit p53-like activities and both p63 and p73 can bind to p53 binding sites when they are overexpressed [78,79]. TAp73 can transactivate many of p53's important target genes such as p21, MDM2, PUMA, NOXA and BAX.…”

Section: The P53 Transcriptional Network and The Cell Death Responsementioning

confidence: 99%

The p53 tumor suppressor network in cancer and the therapeutic modulation of cell death

et al. 2009

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The molecular subversion of cell death is acknowledged as a principal contributor to the development and progression of cancer. The p53 tumor suppressor protein is among the most commonly altered proteins in human cancer. The p53 protein mediates critical functions within cells including the response to genotoxic stress, differentiation, senescence, and cell death. Loss of p53 function can result in enhanced rates of cell proliferation, resistance to cell death stimuli, genomic instability, and metastasis. The community of cancer scientists is now in possession of a vast repository of information regarding the frequency, specific mechanisms, and clinical context of cell death deregulation in cancer. This information has enabled the design of therapeutic agents to target proteins, including p53. The feasibility and impact of targeting cell death signaling proteins has been established in preclinical models of human cancer. The appropriate application of these targeted agents is now being established in clinical trials.

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“…The TAp73 isoforms are generated from an external P1 promoter. The DNp73 proteins are transcribed (a) by the P1 promoter, followed post-transcriptionally by alternative splicing in exons 2 and/or 3 at the 5 ′ end (Stiewe et al, 2002), or (b) by an alternative, internal P2 promoter which generates variants lacking exons 2 and 3, but instead containing an exon 3 ′ that encodes for a unique 13-amino acid domain (Irwin, 2006). Additional complexity is created by alternative splicing in the 3 ′ end, which gives rise to a large number of C-terminal variants of the abovementioned isoforms (Logotheti et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

Image-Based Network Analysis of DNp73 Expression by Immunohistochemistry in Rectal Cancer Patients

et al. 2020

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Background: Rectal cancer is a disease characterized with tumor heterogeneity. The combination of surgery, radiotherapy, and chemotherapy can reduce the risk of local recurrence. However, there is a significant difference in the response to radiotherapy among rectal cancer patients even they have the same tumor stage. Despite rapid advances in knowledge of cellular functions affecting radiosensitivity, there is still a lack of predictive factors for local recurrence and normal tissue damage. The tumor protein DNp73 is thought as a biomarker in colorectal cancer, but its clinical significance is still not sufficiently investigated, mainly due to the limitation of human-based pathology analysis. In this study, we investigated the predictive value of DNp73 in patients with rectal adenocarcinoma using image-based network analysis. Methods: The fuzzy weighted recurrence network of time series was extended to handle multi-channel image data, and applied to the analysis of immunohistochemistry images of DNp73 expression obtained from a cohort of 25 rectal cancer patients who underwent radiotherapy before surgery. Two mathematical weighted network properties, which are the clustering coefficient and characteristic path length, were computed for the image-based networks of the primary tumor (obtained after operation) and biopsy (obtained before operation) of each cancer patient. Results: The ratios of two weighted recurrence network properties of the primary tumors to biopsies reveal the correlation of DNp73 expression and long survival time, and discover the non-effective radiotherapy to a cohort of rectal cancer patients who had short survival time. Conclusion: Our work contributes to the elucidation of the predictive value of DNp73 expression in rectal cancer patients who were given preoperative radiotherapy. Mathematical properties of fuzzy weighted recurrence networks of immunohistochemistry images are not only able to show the predictive factor of DNp73 expression in the patients, but also reveal the identification of non-effective application of radiotherapy to those who had poor overall survival outcome.

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ΔNp73: Misunderstood protein?

Cited by 7 publications

References 19 publications

Overexpressed TP73 induces apoptosis in medulloblastoma

Overexpressed TP73 induces apoptosis in medulloblastoma

The p53 tumor suppressor network in cancer and the therapeutic modulation of cell death

Image-Based Network Analysis of DNp73 Expression by Immunohistochemistry in Rectal Cancer Patients

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