The Experts below are selected from a list of 18870 Experts worldwide ranked by ideXlab platform
Hiroshi Nishina - One of the best experts on this subject based on the ideXlab platform.
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the pdz binding motif of yes associated protein is required for its co activation of tead mediated ctgf transcription and Oncogenic cell transforming activity
Biochemical and Biophysical Research Communications, 2014Co-Authors: Tadanori Shimomura, Norio Miyamura, Shoji Hata, Ryota Miura, Jun Hirayama, Hiroshi NishinaAbstract:Abstract YAP is a transcriptional co-activator that acts downstream of the Hippo signaling pathway and regulates multiple cellular processes, including proliferation. Hippo pathway-dependent phosphorylation of YAP negatively regulates its function. Conversely, attenuation of Hippo-mediated phosphorylation of YAP increases its ability to stimulate proliferation and eventually induces Oncogenic Transformation. The C-terminus of YAP contains a highly conserved PDZ-binding motif that regulates YAP’s functions in multiple ways. However, to date, the importance of the PDZ-binding motif to the Oncogenic cell transforming activity of YAP has not been determined. In this study, we disrupted the PDZ-binding motif in the YAP (5SA) protein, in which the sites normally targeted by Hippo pathway-dependent phosphorylation are mutated. We found that loss of the PDZ-binding motif significantly inhibited the Oncogenic Transformation of cultured cells induced by YAP (5SA). In addition, the increased nuclear localization of YAP (5SA) and its enhanced activation of TEAD-dependent transcription of the cell proliferation gene CTGF were strongly reduced when the PDZ-binding motif was deleted. Similarly, in mouse liver, deletion of the PDZ-binding motif suppressed nuclear localization of YAP (5SA) and YAP (5SA)-induced CTGF expression. Taken together, our results indicate that the PDZ-binding motif of YAP is critical for YAP-mediated oncogenesis, and that this effect is mediated by YAP’s co-activation of TEAD-mediated CTGF transcription.
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the pdz binding motif of yes associated protein is required for its co activation of tead mediated ctgf transcription and Oncogenic cell transforming activity
Biochemical and Biophysical Research Communications, 2014Co-Authors: Tadanori Shimomura, Norio Miyamura, Shoji Hata, Ryota Miura, Jun Hirayama, Hiroshi NishinaAbstract:Abstract YAP is a transcriptional co-activator that acts downstream of the Hippo signaling pathway and regulates multiple cellular processes, including proliferation. Hippo pathway-dependent phosphorylation of YAP negatively regulates its function. Conversely, attenuation of Hippo-mediated phosphorylation of YAP increases its ability to stimulate proliferation and eventually induces Oncogenic Transformation. The C-terminus of YAP contains a highly conserved PDZ-binding motif that regulates YAP’s functions in multiple ways. However, to date, the importance of the PDZ-binding motif to the Oncogenic cell transforming activity of YAP has not been determined. In this study, we disrupted the PDZ-binding motif in the YAP (5SA) protein, in which the sites normally targeted by Hippo pathway-dependent phosphorylation are mutated. We found that loss of the PDZ-binding motif significantly inhibited the Oncogenic Transformation of cultured cells induced by YAP (5SA). In addition, the increased nuclear localization of YAP (5SA) and its enhanced activation of TEAD-dependent transcription of the cell proliferation gene CTGF were strongly reduced when the PDZ-binding motif was deleted. Similarly, in mouse liver, deletion of the PDZ-binding motif suppressed nuclear localization of YAP (5SA) and YAP (5SA)-induced CTGF expression. Taken together, our results indicate that the PDZ-binding motif of YAP is critical for YAP-mediated oncogenesis, and that this effect is mediated by YAP’s co-activation of TEAD-mediated CTGF transcription.
Elizabeth A White - One of the best experts on this subject based on the ideXlab platform.
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ptpn14 degradation by high risk human papillomavirus e7 limits keratinocyte differentiation and contributes to hpv mediated oncogenesis
Proceedings of the National Academy of Sciences of the United States of America, 2019Co-Authors: Joshua Hatterschide, Amelia E Bohidar, Miranda Grace, Tara J Nulton, Hee Won Kim, Brad Windle, Iain M Morgan, Karl Munger, Elizabeth A WhiteAbstract:High-risk human papillomavirus (HPV) E7 proteins enable Oncogenic Transformation of HPV-infected cells by inactivating host cellular proteins. High-risk but not low-risk HPV E7 target PTPN14 for proteolytic degradation, suggesting that PTPN14 degradation may be related to their Oncogenic activity. HPV infects human keratinocytes but the role of PTPN14 in keratinocytes and the consequences of PTPN14 degradation are unknown. Using an HPV16 E7 variant that can inactivate retinoblastoma tumor suppressor (RB1) but cannot degrade PTPN14, we found that high-risk HPV E7-mediated PTPN14 degradation impairs keratinocyte differentiation. Deletion of PTPN14 from primary human keratinocytes decreased keratinocyte differentiation gene expression. Related to Oncogenic Transformation, both HPV16 E7-mediated PTPN14 degradation and PTPN14 deletion promoted keratinocyte survival following detachment from a substrate. PTPN14 degradation contributed to high-risk HPV E6/E7-mediated immortalization of primary keratinocytes and HPV+ but not HPV- cancers exhibit a gene-expression signature consistent with PTPN14 inactivation. We find that PTPN14 degradation impairs keratinocyte differentiation and propose that this contributes to high-risk HPV E7-mediated Oncogenic activity independent of RB1 inactivation.
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ptpn14 degradation by high risk human papillomavirus e7 limits keratinocyte differentiation and contributes to hpv mediated oncogenesis
bioRxiv, 2018Co-Authors: Joshua Hatterschide, Amelia E Bohidar, Miranda Grace, Tara J Nulton, Brad Windle, Iain M Morgan, Karl Munger, Elizabeth A WhiteAbstract:High-risk human papillomavirus (HPV) E7 proteins enable Oncogenic Transformation of HPV-infected cells by inactivating host cellular proteins. High-risk but not low-risk HPV E7 target PTPN14 for proteolytic degradation, suggesting that PTPN14 degradation may be related to their Oncogenic activity. HPV infects human keratinocytes but the role of PTPN14 in keratinocytes and the consequences of PTPN14 degradation are unknown. Using an HPV16 E7 variant that can inactivate RB1 but cannot degrade PTPN14 we found that high-risk HPV E7-mediated PTPN14 degradation impairs keratinocyte differentiation. Deletion of PTPN14 from primary human keratinocytes decreased keratinocyte differentiation gene expression. Related to Oncogenic Transformation, both HPV16 E7-mediated PTPN14 degradation and PTPN14 deletion promoted keratinocyte survival following detachment from a substrate. PTPN14 degradation contributed to high-risk HPV E6/E7-mediated immortalization of primary keratinocytes and HPV-positive but not HPV-negative cancers exhibit a gene expression signature consistent with PTPN14 inactivation. We find that PTPN14 degradation impairs keratinocyte differentiation and propose that this contributes to high-risk HPV E7-mediated Oncogenic activity independent of RB1 inactivation.
Tadanori Shimomura - One of the best experts on this subject based on the ideXlab platform.
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the pdz binding motif of yes associated protein is required for its co activation of tead mediated ctgf transcription and Oncogenic cell transforming activity
Biochemical and Biophysical Research Communications, 2014Co-Authors: Tadanori Shimomura, Norio Miyamura, Shoji Hata, Ryota Miura, Jun Hirayama, Hiroshi NishinaAbstract:Abstract YAP is a transcriptional co-activator that acts downstream of the Hippo signaling pathway and regulates multiple cellular processes, including proliferation. Hippo pathway-dependent phosphorylation of YAP negatively regulates its function. Conversely, attenuation of Hippo-mediated phosphorylation of YAP increases its ability to stimulate proliferation and eventually induces Oncogenic Transformation. The C-terminus of YAP contains a highly conserved PDZ-binding motif that regulates YAP’s functions in multiple ways. However, to date, the importance of the PDZ-binding motif to the Oncogenic cell transforming activity of YAP has not been determined. In this study, we disrupted the PDZ-binding motif in the YAP (5SA) protein, in which the sites normally targeted by Hippo pathway-dependent phosphorylation are mutated. We found that loss of the PDZ-binding motif significantly inhibited the Oncogenic Transformation of cultured cells induced by YAP (5SA). In addition, the increased nuclear localization of YAP (5SA) and its enhanced activation of TEAD-dependent transcription of the cell proliferation gene CTGF were strongly reduced when the PDZ-binding motif was deleted. Similarly, in mouse liver, deletion of the PDZ-binding motif suppressed nuclear localization of YAP (5SA) and YAP (5SA)-induced CTGF expression. Taken together, our results indicate that the PDZ-binding motif of YAP is critical for YAP-mediated oncogenesis, and that this effect is mediated by YAP’s co-activation of TEAD-mediated CTGF transcription.
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the pdz binding motif of yes associated protein is required for its co activation of tead mediated ctgf transcription and Oncogenic cell transforming activity
Biochemical and Biophysical Research Communications, 2014Co-Authors: Tadanori Shimomura, Norio Miyamura, Shoji Hata, Ryota Miura, Jun Hirayama, Hiroshi NishinaAbstract:Abstract YAP is a transcriptional co-activator that acts downstream of the Hippo signaling pathway and regulates multiple cellular processes, including proliferation. Hippo pathway-dependent phosphorylation of YAP negatively regulates its function. Conversely, attenuation of Hippo-mediated phosphorylation of YAP increases its ability to stimulate proliferation and eventually induces Oncogenic Transformation. The C-terminus of YAP contains a highly conserved PDZ-binding motif that regulates YAP’s functions in multiple ways. However, to date, the importance of the PDZ-binding motif to the Oncogenic cell transforming activity of YAP has not been determined. In this study, we disrupted the PDZ-binding motif in the YAP (5SA) protein, in which the sites normally targeted by Hippo pathway-dependent phosphorylation are mutated. We found that loss of the PDZ-binding motif significantly inhibited the Oncogenic Transformation of cultured cells induced by YAP (5SA). In addition, the increased nuclear localization of YAP (5SA) and its enhanced activation of TEAD-dependent transcription of the cell proliferation gene CTGF were strongly reduced when the PDZ-binding motif was deleted. Similarly, in mouse liver, deletion of the PDZ-binding motif suppressed nuclear localization of YAP (5SA) and YAP (5SA)-induced CTGF expression. Taken together, our results indicate that the PDZ-binding motif of YAP is critical for YAP-mediated oncogenesis, and that this effect is mediated by YAP’s co-activation of TEAD-mediated CTGF transcription.
G Chinnadurai - One of the best experts on this subject based on the ideXlab platform.
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modulation of Oncogenic Transformation by the human adenovirus e1a c terminal region
Current Topics in Microbiology and Immunology, 2004Co-Authors: G ChinnaduraiAbstract:The E1A oncogene of human adenoviruses cooperates with other viral and cellular oncogenes in Oncogenic Transformation of primary and established cells. The N-terminal half of E1A proteins that form specific protein complexes with pRb family and p300/CBP transcriptional regulators is essential for the transforming activities of E1A. Although the C-terminal half of E1A is dispensable for the transforming activities, it negatively modulates the Oncogenic activities of the N-terminal region. Mutants of EIA lacking the C-terminal half or a short C-terminal region exhibit a hyper-transforming phenotype in cooperative Transformation assays with the activated ras oncogene. The E1A C-terminal region implicated in the oncogenesis-restraining activity interacts with a 48-kDa cellular phosphoprotein, CtBP, that functions as a transcriptional corepressor. It appears that the C-terminal region of E1A may suppress E1A-mediated Oncogenic Transformation by a dual mechanism of relieving repression cellular genes by CtBP, and also by antagonizing the Oncogenic activities of the N-terminal half of E1A.
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molecular cloning and characterization of a cellular phosphoprotein that interacts with a conserved c terminal domain of adenovirus e1a involved in negative modulation of Oncogenic Transformation
Proceedings of the National Academy of Sciences of the United States of America, 1995Co-Authors: Ute Schaeper, Janice M Boyd, Sulekha Verma, Erik J Uhlmann, T Subramanian, G ChinnaduraiAbstract:Abstract The adenovirus type 2/5 E1A proteins transform primary baby rat kidney (BRK) cells in cooperation with the activated Ras (T24 ras) oncoprotein. The N-terminal half of E1A (exon 1) is essential for this Transformation activity. While the C-terminal half of E1A (exon 2) is dispensable, a region located between residues 225 and 238 of the 243R E1A protein negatively modulates in vitro T24 ras cooperative Transformation as well as the tumorigenic potential of E1A/T24 ras-transformed cells. The same C-terminal domain is also required for binding of a cellular 48-kDa phosphoprotein, C-terminal binding protein (CtBP). We have cloned the cDNA for CtBP via yeast two-hybrid interaction cloning. The cDNA encodes a 439-amino acid (48 kDa) protein that specifically interacts with exon 2 in yeast two-hybrid, in vitro protein binding, and in vivo coimmunoprecipitation analyses. This protein requires residues 225-238 of the 243R E1A protein for interaction. The predicted protein sequence of the isolated cDNA is identical to amino acid sequences obtained from peptides prepared from biochemically purified CtBP. Fine mapping of the CtBP-binding domain revealed that a 6-amino acid motif highly conserved among the E1A proteins of various human and animal adenoviruses is required for this interaction. These results suggest that interaction of CtBP with the E1A proteins may play a critical role in adenovirus replication and Oncogenic Transformation.
Joshua Hatterschide - One of the best experts on this subject based on the ideXlab platform.
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ptpn14 degradation by high risk human papillomavirus e7 limits keratinocyte differentiation and contributes to hpv mediated oncogenesis
Proceedings of the National Academy of Sciences of the United States of America, 2019Co-Authors: Joshua Hatterschide, Amelia E Bohidar, Miranda Grace, Tara J Nulton, Hee Won Kim, Brad Windle, Iain M Morgan, Karl Munger, Elizabeth A WhiteAbstract:High-risk human papillomavirus (HPV) E7 proteins enable Oncogenic Transformation of HPV-infected cells by inactivating host cellular proteins. High-risk but not low-risk HPV E7 target PTPN14 for proteolytic degradation, suggesting that PTPN14 degradation may be related to their Oncogenic activity. HPV infects human keratinocytes but the role of PTPN14 in keratinocytes and the consequences of PTPN14 degradation are unknown. Using an HPV16 E7 variant that can inactivate retinoblastoma tumor suppressor (RB1) but cannot degrade PTPN14, we found that high-risk HPV E7-mediated PTPN14 degradation impairs keratinocyte differentiation. Deletion of PTPN14 from primary human keratinocytes decreased keratinocyte differentiation gene expression. Related to Oncogenic Transformation, both HPV16 E7-mediated PTPN14 degradation and PTPN14 deletion promoted keratinocyte survival following detachment from a substrate. PTPN14 degradation contributed to high-risk HPV E6/E7-mediated immortalization of primary keratinocytes and HPV+ but not HPV- cancers exhibit a gene-expression signature consistent with PTPN14 inactivation. We find that PTPN14 degradation impairs keratinocyte differentiation and propose that this contributes to high-risk HPV E7-mediated Oncogenic activity independent of RB1 inactivation.
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ptpn14 degradation by high risk human papillomavirus e7 limits keratinocyte differentiation and contributes to hpv mediated oncogenesis
bioRxiv, 2018Co-Authors: Joshua Hatterschide, Amelia E Bohidar, Miranda Grace, Tara J Nulton, Brad Windle, Iain M Morgan, Karl Munger, Elizabeth A WhiteAbstract:High-risk human papillomavirus (HPV) E7 proteins enable Oncogenic Transformation of HPV-infected cells by inactivating host cellular proteins. High-risk but not low-risk HPV E7 target PTPN14 for proteolytic degradation, suggesting that PTPN14 degradation may be related to their Oncogenic activity. HPV infects human keratinocytes but the role of PTPN14 in keratinocytes and the consequences of PTPN14 degradation are unknown. Using an HPV16 E7 variant that can inactivate RB1 but cannot degrade PTPN14 we found that high-risk HPV E7-mediated PTPN14 degradation impairs keratinocyte differentiation. Deletion of PTPN14 from primary human keratinocytes decreased keratinocyte differentiation gene expression. Related to Oncogenic Transformation, both HPV16 E7-mediated PTPN14 degradation and PTPN14 deletion promoted keratinocyte survival following detachment from a substrate. PTPN14 degradation contributed to high-risk HPV E6/E7-mediated immortalization of primary keratinocytes and HPV-positive but not HPV-negative cancers exhibit a gene expression signature consistent with PTPN14 inactivation. We find that PTPN14 degradation impairs keratinocyte differentiation and propose that this contributes to high-risk HPV E7-mediated Oncogenic activity independent of RB1 inactivation.
