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Jennifer A. Byrne - One of the best experts on this subject based on the ideXlab platform.
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Dropping in on the lipid droplet- Tumor Protein D52 (TPD52) as a new regulator and resident Protein.
Adipocyte, 2016Co-Authors: Yuyan Chen, Sarah Frost, Jennifer A. ByrneAbstract:ABSTRACTLipid droplets are essential for both the storage and retrieval of excess cellular nutrients, and their biology is regulated by a diverse range of cellular Proteins, some of which function at the lipid droplet. Numerous studies have characterized lipid droplet proteomes in different organisms and cell types, and RNAi whole genome screening studies have examined the genetic regulation of lipid storage in C. elegans and D. melanogaster. While Tumor Protein D52 (TPD52) did not emerge from earlier studies as a strong candidate, exogenous expression of human TPD52 in cultured cells resulted in significantly increased numbers of lipid droplets, and oleic acid supplementation increased TPD52 detection at both lipid droplets and the Golgi apparatus. These results suggest that direct testing of Proteins that are infrequently but recurrently identified in proteomic and RNAi screening studies may identify novel lipid droplet regulators. While the analysis of these possibly lower-abundance or itinerant lipid ...
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Tumor Protein D52 (TPD52) and cancer—oncogene understudy or understudied oncogene?
Tumor Biology, 2014Co-Authors: Jennifer A. Byrne, Sarah Frost, Yuyan Chen, Robert K. BrightAbstract:The Tumor Protein D52 (TPD52) gene was identified nearly 20 years ago through its overexpression in human cancer, and a substantial body of data now strongly supports TPD52 representing a gene amplification target at chromosome 8q21.13. This review updates progress toward understanding the significance of TPD52 overexpression and targeting, both in Tumors known to be characterized by TPD52 overexpression/amplification, and those where TPD52 overexpression/amplification has been recently or variably reported. We highlight recent findings supporting microRNA regulation of TPD52 expression in experimental systems and describe progress toward deciphering TPD52’s cellular functions, particularly in cancer cells. Finally, we provide an overview of TPD52’s potential as a cancer biomarker and immunotherapeutic target. These combined studies highlight the potential value of genes such as TPD52, which are overexpressed in many cancer types, but have been relatively understudied.
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Tumor Protein D52 represents a negative regulator of ATM Protein levels.
Cell Cycle, 2013Co-Authors: Yuyan Chen, Guy E Groblewski, Alvin Kamili, Jayne R. Hardy, Kum Kum Khanna, Jennifer A. ByrneAbstract:Tumor Protein D52 (TPD52) is a coiled-coil motif bearing hydrophilic polypeptide known to be overexpressed in cancers of diverse cellular origins. Increased TPD52 expression is associated with increased proliferation and invasive capacity in different cell types. Recent studies have reported a correlation between TPD52 transcript levels and G2 chromosomal radiosensitivity in lymphocytes of women at risk of hereditary breast cancer, and that TPD52 knockdown significantly reduced the radiation sensitivity of multiple cancer cell lines. In this study, we investigated possible roles for TPD52 in DNA damage response, and found that increased TPD52 expression in breast cancer and TPD52-expressing BALB/c 3T3 cells compromised ATM-mediated cellular responses to DNA double-strand breaks induced by γ-ray irradiation, which was associated with downregulation of steady-state ATM Protein, but not transcript levels, regardless of irradiation status. TPD52-expressing 3T3 cells also showed significantly increased radiati...
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TPD52 (Tumor Protein D52)
Atlas of Genetics and Cytogenetics in Oncology and Haematology, 2011Co-Authors: Austin Della-franca, Jennifer A. ByrneAbstract:Review on TPD52 (Tumor Protein D52), with data on DNA, on the Protein encoded, and where the gene is implicated.
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Tumor Protein d52 expression and ca2 dependent phosphorylation modulates lysosomal membrane Protein trafficking to the plasma membrane
American Journal of Physiology-cell Physiology, 2010Co-Authors: Diana D H Thomas, Christina L Martin, Jennifer A. Byrne, Ning Weng, Guy E GroblewskiAbstract:Tumor Protein D52 (also known as CRHSP-28) is highly expressed in multiple cancers and Tumor-derived cell lines; however, it is normally abundant in secretory epithelia throughout the digestive sys...
Edward A. Ratovitski - One of the best experts on this subject based on the ideXlab platform.
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Tumor Protein p63 microrna network in epithelial cancer cells
Current Genomics, 2013Co-Authors: Edward A. RatovitskiAbstract:Non-coding microRNAs are involved in multiple regulatory mechanisms underlying response of cancer cells to stress leading to apoptosis, cell cycle arrest and autophagy. Many molecular layers are implicated in such cellular response including epigenetic regulation of transcription, RNA processing, metabolism, signaling. The molecular interrelationship between Tumor Protein (TP)-p53 family members and specific microRNAs is a key functional network supporting Tumor cell response to chemotherapy and potentially playing a decisive role in chemoresistance of human epithelial cancers. TP63 was shown to modulate the expression of numerous microRNAs involved in regulation of epithelial cell proliferation, differentiation, senescence, “stemness” and skin maintenance, epithelial/ mesenchymal transition, and Tumorigenesis in several types of epithelial cancers (e.g. squamous cell carcinoma, ovarian carcinoma, prostate carcinoma, gastric cancer, bladder cancer, and breast Tumors), as well as in chemoresistance of cancer cells. TP63/microRNA network was shown to be involved in cell cycle arrest, apoptosis, autophagy, metabolism and epigenetic transcriptional regulation, thereby providing the groundwork for novel chemotherapeutic venues.
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Tumor Protein p63/microRNA Network in Epithelial Cancer Cells.
Current Genomics, 2013Co-Authors: Edward A. RatovitskiAbstract:Non-coding microRNAs are involved in multiple regulatory mechanisms underlying response of cancer cells to stress leading to apoptosis, cell cycle arrest and autophagy. Many molecular layers are implicated in such cellular response including epigenetic regulation of transcription, RNA processing, metabolism, signaling. The molecular interrelationship between Tumor Protein (TP)-p53 family members and specific microRNAs is a key functional network supporting Tumor cell response to chemotherapy and potentially playing a decisive role in chemoresistance of human epithelial cancers. TP63 was shown to modulate the expression of numerous microRNAs involved in regulation of epithelial cell proliferation, differentiation, senescence, “stemness” and skin maintenance, epithelial/ mesenchymal transition, and Tumorigenesis in several types of epithelial cancers (e.g. squamous cell carcinoma, ovarian carcinoma, prostate carcinoma, gastric cancer, bladder cancer, and breast Tumors), as well as in chemoresistance of cancer cells. TP63/microRNA network was shown to be involved in cell cycle arrest, apoptosis, autophagy, metabolism and epigenetic transcriptional regulation, thereby providing the groundwork for novel chemotherapeutic venues.
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Tumor Protein p63 is a key regulator of skin functions in ectodermal dysplasia
2013Co-Authors: Edward A. RatovitskiAbstract:Tumor Protein (TP)-p63 has been discovered as TP53 homolog more than fifteen years ago and has become a master regulator of skin development, proliferation and stem cell maintenance. While TP53 is known to be the most mutated gene in human cancer, TP63 mutations are mostly associated with the various types of ectodermal dysplasia. All TP53 family members, TP53, TP63 and TP73, function as transcription factors that regulate the cell cycle arrest, apoptosis, autophagy or metabolism through activation/repression of downstream target genes or Protein-Protein interactions with other Protein regulators of transcription and splicing. Several downstream target genes or Protein interactors of TP63 are involved in the molecular mechanisms underlying the ectodermal dysplasia phenotypes. This mini-review underlines a few venues of investigations about the key role for TP63 in skin biology and pathology.
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global Tumor Protein p53 p63 interactome making a case for cisplatin chemoresistance
Cell Cycle, 2012Co-Authors: Yiping Huang, Jun Seop Jeong, Jun Okamura, Myoung Sookkim, Rafael Guerreropreston, Edward A. RatovitskiAbstract:Cisplatin chemoresistance is a clinical problem that leads to treatment failure in various human epithelial cancers. Members of Tumor Protein (TP) p53 family play various critical roles in the multiple molecular mechanisms underlying the chemoresistance of Tumor cells. However, the in-depth mechanisms of the cellular response to cisplatin-induced cell death are still under thorough investigation. We previously showed that squamous cell carcinoma (SCC) cells exposed to cisplatin display an ATM-dependent phosphorylation of ΔNp63α, leading to a specific function of the phosphorylated (p)-ΔNp63α transcription factor in cisplatin-sensitive Tumor cells. We further found that SCC cells expressing non-p-ΔNp63α-S385G became cisplatin-resistant. Using quantitative mass-spectrometry of Protein complexes labeled with isobaric tags, we showed that TP53 and ΔNp63α are involved in numerous Protein-Protein interactions, which are likely to be implicated in the response of Tumor cells to cisplatin exposure. We found that p-ΔNp63α binds to the splicing complex, leading to repression of mRNA splicing and activation of ACIN1-mediated cell death pathway. In contrast to p-ΔNp63α, non-p-ΔNp63α fails to bind the critical members of the splicing complex, thereby leading to activation of RNA splicing and reduction of cell death pathway. Overall, our studies provide an integrated proteomic platform in making a case for the role of the p53/p63 interactome in cisplatin chemoresistance.
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Tumor Protein p63/nuclear factor κB feedback loop in regulation of cell death.
Journal of Biological Chemistry, 2011Co-Authors: Yiping Huang, Debasish Sinha, Edward A. Ratovitski, David SidranskyAbstract:Tumor Protein (TP)-p53 family members often play proapoptotic roles, whereas nuclear factor kappa B (NF-kappa B) functions as a proapoptotic and antiapoptotic regulator depending on the cellular environment. We previously showed that the NF-kappa B activation leads to the reduction of the TP63 isoform, Delta Np63 alpha, thereby rendering the cells susceptible to cell death upon DNA damage. However, the functional relationship between TP63 isotypes and NF-kappa B is poorly understood. Here, we report that the TAp63 regulates NF-kappa B transcription and Protein stability subsequently leading to the cell death phenotype. We found that TAp63 beta induced the expression of the p65 subunit of NF-kappa B (RELA) and target genes involved in cell cycle arrest or apoptosis, thereby triggering cell death pathways in MCF10A cells. RELA was shown to concomitantly modulate specific cell survival pathways, making it indispensable for the TAp63 beta-dependent regulation of cell death. We showed that TAp63 beta and RELA formed Protein complexes resulted in their mutual stabilization and inhibition of the RELA ubiquitination. Finally, we showed that TAp63 beta directly induced RelA transcription by binding to and activating of its promoter and, in turn, leading to activation of the NF-kappa B-dependent cell death genes. Overall, our data defined the regulatory feedback loop between TAp63 beta and NF-kappa B involved in the activation of cell death process of cancer cells.
Karin M. Kirschner - One of the best experts on this subject based on the ideXlab platform.
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wilms Tumor Protein wt1 regulates the interleukin 10 il 10 gene
FEBS Letters, 2010Co-Authors: Lina K Sciesielski, Karin M. Kirschner, Holger Scholz, Anja Bondke PerssonAbstract:We identified the Wilms’ Tumor Protein, Wt1, as a novel transcriptional activator of the immunosuppressant cytokine interleukin-10 (IL-10). Silencing of Wt1 by RNA interference reduced IL-10 mRNA levels by approximately 90%. IL-10 transcripts were increased more than 15-fold upon forced expression of Wt1. Electrophoretic mobility shift assay and chromatin immunoprecipitation revealed a cis-element that was responsible for activation of the IL-10 promoter by Wt1 in murine macrophages. Mutation of the Wt1 binding motif abrogated stimulation of the IL-10 promoter by Tumor necrosis factor-α (TNFα). These results suggest a novel immune regulatory function of Wt1 in controlling IL-10 gene expression.
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Wilms' Tumor Protein ( KTS) modulates renin gene
2008Co-Authors: Alexander Paliege, Anja Bondke, Karin M. Kirschner, Peter Martinka, Charlotte Kaps, Andreas Patzak, Pontus B. Persson, Bernd J. Thiele, Holger Scholz, Ralf MrowkaAbstract:Renin plays a crucial role in the control of various physiological processes such as blood pressure and body fluid homeostasis. Here, we show that a splice variant of the Wilms’ Tumor Protein lacking three amino acids WT1(� KTS) suppresses renin gene transcription. Using bioinformatics tools, we initially predicted that a WT1-binding site exists in a regulatory region about 12 kb upstream of the renin promoter; this was confirmed by reporter gene assays and gel shift experiments in heterologous cells. Co-expression of Wt1 and renin Proteins was found in rat kidney sections, mouse kidney blood vessels, and a cell line derived from the juxtaglomerular apparatus that produces renin. Knockdown of WT1 Protein by siRNA significantly increased the cellular renin mRNA content, while overexpression of WT1(� KTS) reduced renin gene expression in stable and transiently transfected cells. A mutant WT1(� KTS) Protein found in Wilms’ Tumors failed to suppress renin gene reporter activity and endogenous renin expression. Our findings show that renin gene transcription is regulated by the WT1(� KTS) Protein and this may explain findings in patients with WT1 gene mutations of increased plasma renin and hypertension.
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Wilms' Tumor Protein (-KTS) modulates renin gene transcription.
Kidney International, 2008Co-Authors: Andreas Steege, Alexander Paliege, Anja Bondke, Karin M. Kirschner, Peter Martinka, Charlotte Kaps, Andreas Patzak, Pontus B. Persson, Michael Fähling, Bernd J. ThieleAbstract:Renin plays a crucial role in the control of various physiological processes such as blood pressure and body fluid homeostasis. Here, we show that a splice variant of the Wilms' Tumor Protein lacking three amino acids WT1(−KTS) suppresses renin gene transcription. Using bioinformatics tools, we initially predicted that a WT1-binding site exists in a regulatory region about 12kb upstream of the renin promoter; this was confirmed by reporter gene assays and gel shift experiments in heterologous cells. Co-expression of Wt1 and renin Proteins was found in rat kidney sections, mouse kidney blood vessels, and a cell line derived from the juxtaglomerular apparatus that produces renin. Knockdown of WT1 Protein by siRNA significantly increased the cellular renin mRNA content, while overexpression of WT1(−KTS) reduced renin gene expression in stable and transiently transfected cells. A mutant WT1(−KTS) Protein found in Wilms' Tumors failed to suppress renin gene reporter activity and endogenous renin expression. Our findings show that renin gene transcription is regulated by the WT1(−KTS) Protein and this may explain findings in patients with WT1 gene mutations of increased plasma renin and hypertension.
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Wilms' Tumor Protein (-KTS) modulates renin gene transcription. Commentary
Kidney International, 2008Co-Authors: Jordan A. Kreidberg, Alexander Paliege, Anja Bondke, Karin M. Kirschner, Peter Martinka, Charlotte Kaps, Andreas Steege, Michael Fähling, Sunny Hartwig, Andreas PatzakAbstract:Renin plays a crucial role in the control of various physiological processes such as blood pressure and body fluid homeostasis. Here, we show that a splice variant of the Wilms' Tumor Protein lacking three amino acids WT1(-KTS) suppresses renin gene transcription. Using bioinformatics tools, we initially predicted that a WT1-binding site exists in a regulatory region about 12kb upstream of the renin promoter; this was confirmed by reporter gene assays and gel shift experiments in heterologous cells. Co-expression of Wt1 and renin Proteins was found in rat kidney sections, mouse kidney blood vessels, and a cell line derived from the juxtaglomerular apparatus that produces renin. Knockdown of WT1 Protein by siRNA significantly increased the cellular renin mRNA content, while overexpression of WT1(-KTS) reduced renin gene expression in stable and transiently transfected cells. A mutant WT1-KTS) Protein found in Wilms' Tumors failed to suppress renin gene reporter activity and endogenous renin expression. Our findings show that renin gene transcription is regulated by the WTI1-KTS) Protein and this may explain findings in patients with WT1 gene mutations of increased plasma renin and hypertension.
Anja Bondke Persson - One of the best experts on this subject based on the ideXlab platform.
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wilms Tumor Protein wt1 regulates the interleukin 10 il 10 gene
FEBS Letters, 2010Co-Authors: Lina K Sciesielski, Karin M. Kirschner, Holger Scholz, Anja Bondke PerssonAbstract:We identified the Wilms’ Tumor Protein, Wt1, as a novel transcriptional activator of the immunosuppressant cytokine interleukin-10 (IL-10). Silencing of Wt1 by RNA interference reduced IL-10 mRNA levels by approximately 90%. IL-10 transcripts were increased more than 15-fold upon forced expression of Wt1. Electrophoretic mobility shift assay and chromatin immunoprecipitation revealed a cis-element that was responsible for activation of the IL-10 promoter by Wt1 in murine macrophages. Mutation of the Wt1 binding motif abrogated stimulation of the IL-10 promoter by Tumor necrosis factor-α (TNFα). These results suggest a novel immune regulatory function of Wt1 in controlling IL-10 gene expression.
Holger Scholz - One of the best experts on this subject based on the ideXlab platform.
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wilms Tumor Protein wt1 regulates the interleukin 10 il 10 gene
FEBS Letters, 2010Co-Authors: Lina K Sciesielski, Karin M. Kirschner, Holger Scholz, Anja Bondke PerssonAbstract:We identified the Wilms’ Tumor Protein, Wt1, as a novel transcriptional activator of the immunosuppressant cytokine interleukin-10 (IL-10). Silencing of Wt1 by RNA interference reduced IL-10 mRNA levels by approximately 90%. IL-10 transcripts were increased more than 15-fold upon forced expression of Wt1. Electrophoretic mobility shift assay and chromatin immunoprecipitation revealed a cis-element that was responsible for activation of the IL-10 promoter by Wt1 in murine macrophages. Mutation of the Wt1 binding motif abrogated stimulation of the IL-10 promoter by Tumor necrosis factor-α (TNFα). These results suggest a novel immune regulatory function of Wt1 in controlling IL-10 gene expression.
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Wilms' Tumor Protein ( KTS) modulates renin gene
2008Co-Authors: Alexander Paliege, Anja Bondke, Karin M. Kirschner, Peter Martinka, Charlotte Kaps, Andreas Patzak, Pontus B. Persson, Bernd J. Thiele, Holger Scholz, Ralf MrowkaAbstract:Renin plays a crucial role in the control of various physiological processes such as blood pressure and body fluid homeostasis. Here, we show that a splice variant of the Wilms’ Tumor Protein lacking three amino acids WT1(� KTS) suppresses renin gene transcription. Using bioinformatics tools, we initially predicted that a WT1-binding site exists in a regulatory region about 12 kb upstream of the renin promoter; this was confirmed by reporter gene assays and gel shift experiments in heterologous cells. Co-expression of Wt1 and renin Proteins was found in rat kidney sections, mouse kidney blood vessels, and a cell line derived from the juxtaglomerular apparatus that produces renin. Knockdown of WT1 Protein by siRNA significantly increased the cellular renin mRNA content, while overexpression of WT1(� KTS) reduced renin gene expression in stable and transiently transfected cells. A mutant WT1(� KTS) Protein found in Wilms’ Tumors failed to suppress renin gene reporter activity and endogenous renin expression. Our findings show that renin gene transcription is regulated by the WT1(� KTS) Protein and this may explain findings in patients with WT1 gene mutations of increased plasma renin and hypertension.
