The Experts below are selected from a list of 1680822 Experts worldwide ranked by ideXlab platform
N B La Thangue - One of the best experts on this subject based on the ideXlab platform.
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functional synergy between dp 1 and e2f 1 in the cell cycle regulating transcription factor drtf1 e2f
The EMBO Journal, 1993Co-Authors: L R Bandara, M Zamanian, Vicky Buck, Leland H Johnston, N B La ThangueAbstract:It is widely believed that the cellular transcription factor DRTF1/E2F integrates cell cycle events with the transcription apparatus because during cell cycle progression in mammalian cells it interacts with molecules that are important regulators of cellular proliferation, such as the retinoblastoma tumour suppressor gene product (pRb), P107, cyclins and cyclin-dependent kinases. Thus, pRb, which negatively regulates early cell cycle progression and is frequently mutated in tumour cells, and the Rb-related Protein P107, bind to and repress the transcriptional activity of DRTF1/E2F. Viral oncoProteins, such as adenovirus E1a and SV40 large T antigen, overcome such repression by sequestering pRb and P107 and in so doing are likely to activate genes regulated by DRTF1/E2F, such as cdc2, c-myc and DHFR. Two sequence-specific DNA binding Proteins, E2F-1 and DP-1, which bind to the E2F site, contain a small region of similarity. The functional relationship between them has, however, been unclear. We report here that DP-1 and E2F-1 exist in a DNA binding complex in vivo and that they bind efficiently and preferentially as a heterodimer to the E2F site. Moreover, studies in yeast and Drosophila cells indicate that DP-1 and E2F-1 interact synergistically in E2F site-dependent transcriptional activation.
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transcriptional repression by the rb related Protein P107
Molecular Biology of the Cell, 1993Co-Authors: M Zamanian, N B La ThangueAbstract:The transcription factor DRTF1/E2F is believed to play an important role in regulating cellular proliferation because it undergoes a series of periodic interactions with Proteins that are known to ...
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a new component of the transcription factor drtf1 e2f
Nature, 1993Co-Authors: R Girling, Janet F Partridge, L R Bandara, N Burden, N F Totty, Justin J Hsuan, N B La ThangueAbstract:Transcription factor DRTF1/E2F coordinates events in the cell cycle with transcription by its cyclical interactions with important regulators of cellular proliferation like the retinoblastoma tumour-suppressor gene product (Rb) and the Rb-related Protein, P107 (refs 1-8). DRTF1/E2F binding sites occur in the control regions of genes involved in proliferation, and both Rb and P107 repress the capacity of DRTF1/E2F to activate transcription (refs 11, 12; M. Zamanian and N.B.L.T., manuscript submitted). Mutant Rb Proteins isolated from tumour cells are unable to bind DRTF1/E2F (refs 11-13), and certain viral oncoProteins, such as adenovirus E1A, sequester Rb and P107 in order to free active DRTF1/E2F (refs 5, 11, 12, 14, 15). Here we report the isolation of a complementary DNA encoding DRTF1-polypeptide-1 (DP-1), a major sequence-specific binding Protein that is present in DRTF1/E2F, including Rb- and P107-associated DRTF1/E2F. The DNA-binding domain of DP-1 contains a region that resembles that of E2F-1 (refs 16, 17), and recognizes the same sequence. DRTF1/E2F thus appears to contain at least two sequence-specific DNA-binding Proteins.
Elizabeth M Wilson - One of the best experts on this subject based on the ideXlab platform.
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proto oncogene activity of melanoma antigen a11 mage a11 regulates retinoblastoma related P107 and e2f1 Proteins
Journal of Biological Chemistry, 2013Co-Authors: Shifeng Su, John T. Minges, Amanda J. Blackwelder, Gail Grossman, James L Mohler, Elizabeth M WilsonAbstract:Melanoma antigen-A11 (MAGE-A11) is a low-abundance, primate-specific steroid receptor coregulator in normal tissues of the human reproductive tract that is expressed at higher levels in prostate cancer. Increased expression of MAGE-A11 enhances androgen receptor transcriptional activity and promotes prostate cancer cell growth. Further investigation into the mechanisms of MAGE-A11 function in prostate cancer demonstrated interactions with the retinoblastoma-related Protein P107 and Rb tumor suppressor but no interaction with p130 of the Rb family. MAGE-A11 interaction with P107 was associated with transcriptional repression in cells with low MAGE-A11 and transcriptional activation in cells with higher MAGE-A11. Selective interaction of MAGE-A11 with retinoblastoma family members suggested the regulation of E2F transcription factors. MAGE-A11 stabilized P107 by inhibition of ubiquitination and linked P107 to hypophosphorylated E2F1 in association with the stabilization and activation of E2F1. The androgen receptor and MAGE-A11 modulated endogenous expression of the E2F1-regulated cyclin-dependent kinase inhibitor p27Kip1. The ability of MAGE-A11 to increase E2F1 transcriptional activity was similar to the activity of adenovirus early oncoProtein E1A and depended on MAGE-A11 interactions with P107 and p300. The immunoreactivity of P107 and MAGE-A11 was greater in advanced prostate cancer than in benign prostate, and knockdown with small inhibitory RNA showed that P107 is a transcriptional activator in prostate cancer cells. These results suggest that MAGE-A11 is a proto-oncogene whose increased expression in prostate cancer reverses retinoblastoma-related Protein P107 from a transcriptional repressor to a transcriptional activator of the androgen receptor and E2F1.
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proto oncogene activity of melanoma antigen a11 mage a11 regulates retinoblastoma related P107 and e2f1 Proteins
Journal of Biological Chemistry, 2013Co-Authors: John T. Minges, Amanda J. Blackwelder, Gail Grossman, James L Mohler, Elizabeth M WilsonAbstract:Melanoma antigen-A11 (MAGE-A11) is a low-abundance, primate-specific steroid receptor coregulator in normal tissues of the human reproductive tract that is expressed at higher levels in prostate cancer. Increased expression of MAGE-A11 enhances androgen receptor transcriptional activity and promotes prostate cancer cell growth. Further investigation into the mechanisms of MAGE-A11 function in prostate cancer demonstrated interactions with the retinoblastoma-related Protein P107 and Rb tumor suppressor but no interaction with p130 of the Rb family. MAGE-A11 interaction with P107 was associated with transcriptional repression in cells with low MAGE-A11 and transcriptional activation in cells with higher MAGE-A11. Selective interaction of MAGE-A11 with retinoblastoma family members suggested the regulation of E2F transcription factors. MAGE-A11 stabilized P107 by inhibition of ubiquitination and linked P107 to hypophosphorylated E2F1 in association with the stabilization and activation of E2F1. The androgen receptor and MAGE-A11 modulated endogenous expression of the E2F1-regulated cyclin-dependent kinase inhibitor p27Kip1. The ability of MAGE-A11 to increase E2F1 transcriptional activity was similar to the activity of adenovirus early oncoProtein E1A and depended on MAGE-A11 interactions with P107 and p300. The immunoreactivity of P107 and MAGE-A11 was greater in advanced prostate cancer than in benign prostate, and knockdown with small inhibitory RNA showed that P107 is a transcriptional activator in prostate cancer cells. These results suggest that MAGE-A11 is a proto-oncogene whose increased expression in prostate cancer reverses retinoblastoma-related Protein P107 from a transcriptional repressor to a transcriptional activator of the androgen receptor and E2F1. Background: Primate-specific melanoma antigen-A11 (MAGE-A11) increases steroid receptor transcriptional activity and enhances prostate cancer cell growth. Results: MAGE-A11 activates E2F1 by interacting with retinoblastoma-related Protein P107. Conclusion: MAGE-A11 influences cell cycle regulatory pathways in a molecular hub for transcription. Significance: MAGE-A11 is a proto-oncogene whose increased expression impacts multiple signaling mechanisms that contribute to prostate cancer growth and progression.
Ed Harlow - One of the best experts on this subject based on the ideXlab platform.
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the prb related Protein P107 contains two growth suppression domains independent interactions with e2f and cyclin cdk complexes
The EMBO Journal, 1995Co-Authors: Liang Zhu, Greg H Enders, Jacqueline A Lees, Roderick L Beijersbergen, Rene Bernards, Ed HarlowAbstract:Abstract Unregulated expression of either the retinoblastoma Protein (pRB) or the related Protein P107 can cause growth arrest of sensitive cells in the G1 phase of the cell cycle. However, growth arrests mediated by P107 and pRB are not identical. Through structure-function and co-expression analyses we have dissected the P107 molecule into two domains that independently are able to block cell cycle progression. One domain corresponds to the sequences needed for interaction with the transcription factor E2F, and the other corresponds to the interaction domain for cyclin A or cyclin E complexes. In cervical carcinoma cell line C33A, which was previously shown to be sensitive to P107 but resistant to pRB growth suppression, only the cyclin binding domain is active as a growth suppressor. Furthermore, we show that these two independent domains are functional in untransformed mouse fibroblasts. Together, these results provide experimental evidence for the presence of two functional domains in P107 and pinpoint an important functional difference between P107 and pRB.
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inhibition of cell proliferation by P107 a relative of the retinoblastoma Protein
Genes & Development, 1993Co-Authors: S Van Den Heuvel, Mark E Ewen, David M Livingston, Nicholas J Dyson, Kristian Helin, Ali Fattaey, Ed HarlowAbstract:The cellular Protein P107 shares many structural and biochemical features with the retinoblastoma gene product, pRB. We have isolated a full-length cDNA for human P107 and have used this clone to study the function of P107. We show that, like pRB, P107 is a potent inhibitor of E2F-mediated trans-activation, and overexpression of P107 can inhibit proliferation in certain cell types, arresting sensitive cells in G 1 . Several experiments, however, showed that growth inhibition by pRB and P107 did not occur through the same mechanism. First, in the cervical carcinoma cell line C33A, P107 was able to block cell proliferation, whereas pRB could not, even though both Proteins were potent inhibitors of E2F-mediated transcription in this cell line
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inhibition of cell proliferation by P107 a relative of the retinoblastoma Protein
Genes & Development, 1993Co-Authors: S Van Den Heuvel, Mark E Ewen, David M Livingston, Nicholas J Dyson, Kristian Helin, Ali Fattaey, Ed HarlowAbstract:: The cellular Protein P107 shares many structural and biochemical features with the retinoblastoma gene product, pRB. We have isolated a full-length cDNA for human P107 and have used this clone to study the function of P107. We show that, like pRB, P107 is a potent inhibitor of E2F-mediated trans-activation, and overexpression of P107 can inhibit proliferation in certain cell types, arresting sensitive cells in G1. Several experiments, however, showed that growth inhibition by pRB and P107 did not occur through the same mechanism. First, in the cervical carcinoma cell line C33A, P107 was able to block cell proliferation, whereas pRB could not, even though both Proteins were potent inhibitors of E2F-mediated transcription in this cell line. Second, growth arrest by pRB and P107 was rescued differentially by various cell cycle regulators. Third, some mutants of P107 that cannot associate with adenovirus E1A were still able to inhibit cell proliferation, whereas analogous mutants in pRB are known to be unable to block cell growth. Together, these results suggest a biological role of P107 that is related, but not identical, to that of pRB.
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independent binding of the retinoblastoma Protein and P107 to the transcription factor e2f
Nature, 1992Co-Authors: Liang Cao, B Faha, Marlene Dembski, Lihuei Tsai, Ed Harlow, Nicholas J DysonAbstract:The cellular Protein P107 and the retinoblastoma Protein (pRB) have many features in common. Most strikingly, they contain homologous Protein domains that mediate interaction with the oncoProteins of several small DNA tumour viruses, including adenovirus E1A and SV40 large-T antigen. In cells that do not contain these viral oncoProteins, pRB interacts with the cellular transcription factor E2F or a related Protein termed DRTF1. E2F associates with a form of pRB that is found primarily in G1 cells. It seems that the E2F-pRB complex dissociates near the G1-S boundary before the initiation of S phase, releasing free E2F and apparently stimulating the ability of E2F to activate transcription. Cells that express E1A have no or little pRB-E2F complex, presumably because of the association of E1A with pRB. During S phase, E2F forms a second complex that contains cyclin A but apparently lacks pRB. Here, we report that P107 is found in the cyclin A/E2F complex and that this complex also contains p33cdk2. These observations suggest that P107 and pRB cooperate in the regulation of E2F activity, each affecting different stages of the cell cycle. Thus, by binding to pRB and P107, E1A and large-T antigen target two distinct aspects of E2F regulation.
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independent binding of the retinoblastoma Protein and P107 to the transcription factor e2f
Nature, 1992Co-Authors: B Faha, Marlene Dembski, Lihuei Tsai, Ed Harlow, Nicholas J DysonAbstract:THE cellular Protein P107 and the retinoblastoma Protein (pRB) have many features in common. Most strikingly, they contain homologous Protein domains that mediate interaction with the oncoProteins of several small DNA tumour viruses, including adenovirus El A and SV40 large-T antigen1–9. In cells that do not contain these viral oncoProteins, pRB interacts with the cellular transcription factor E2F (refs 10–12) or a related Protein termed DRTF1 (ref. 13). E2F associates with a form of pRB that is found primarily in Gl cells10. It seems that the E2F-pRB complex dissociates near the Gl-S boundary before the initiation of S phase, releasing free E2F and apparently stimulating the ability of E2F to activate transcription14. Cells that express E1A have no or little pRB-E2F complex, presumably because of the association of E1A with pRB10–15. During S phase, E2F forms a second complex that contains cyclin A but apparently lacks pRB15. Here, we report that P107 is found in the cyclin A/E2F complex and that this complex also contains p33cdk2. These observations suggest that P107 and pRB cooperate in the regulation of E2F activity, each affecting different stages of the cell cycle. Thus, by binding to pRB and pi 07, El A and large-T antigen target two distinct aspects of E2F regulation.
Nicholas J Dyson - One of the best experts on this subject based on the ideXlab platform.
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inhibition of cell proliferation by P107 a relative of the retinoblastoma Protein
Genes & Development, 1993Co-Authors: S Van Den Heuvel, Mark E Ewen, David M Livingston, Nicholas J Dyson, Kristian Helin, Ali Fattaey, Ed HarlowAbstract:The cellular Protein P107 shares many structural and biochemical features with the retinoblastoma gene product, pRB. We have isolated a full-length cDNA for human P107 and have used this clone to study the function of P107. We show that, like pRB, P107 is a potent inhibitor of E2F-mediated trans-activation, and overexpression of P107 can inhibit proliferation in certain cell types, arresting sensitive cells in G 1 . Several experiments, however, showed that growth inhibition by pRB and P107 did not occur through the same mechanism. First, in the cervical carcinoma cell line C33A, P107 was able to block cell proliferation, whereas pRB could not, even though both Proteins were potent inhibitors of E2F-mediated transcription in this cell line
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inhibition of cell proliferation by P107 a relative of the retinoblastoma Protein
Genes & Development, 1993Co-Authors: S Van Den Heuvel, Mark E Ewen, David M Livingston, Nicholas J Dyson, Kristian Helin, Ali Fattaey, Ed HarlowAbstract:: The cellular Protein P107 shares many structural and biochemical features with the retinoblastoma gene product, pRB. We have isolated a full-length cDNA for human P107 and have used this clone to study the function of P107. We show that, like pRB, P107 is a potent inhibitor of E2F-mediated trans-activation, and overexpression of P107 can inhibit proliferation in certain cell types, arresting sensitive cells in G1. Several experiments, however, showed that growth inhibition by pRB and P107 did not occur through the same mechanism. First, in the cervical carcinoma cell line C33A, P107 was able to block cell proliferation, whereas pRB could not, even though both Proteins were potent inhibitors of E2F-mediated transcription in this cell line. Second, growth arrest by pRB and P107 was rescued differentially by various cell cycle regulators. Third, some mutants of P107 that cannot associate with adenovirus E1A were still able to inhibit cell proliferation, whereas analogous mutants in pRB are known to be unable to block cell growth. Together, these results suggest a biological role of P107 that is related, but not identical, to that of pRB.
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independent binding of the retinoblastoma Protein and P107 to the transcription factor e2f
Nature, 1992Co-Authors: Liang Cao, B Faha, Marlene Dembski, Lihuei Tsai, Ed Harlow, Nicholas J DysonAbstract:The cellular Protein P107 and the retinoblastoma Protein (pRB) have many features in common. Most strikingly, they contain homologous Protein domains that mediate interaction with the oncoProteins of several small DNA tumour viruses, including adenovirus E1A and SV40 large-T antigen. In cells that do not contain these viral oncoProteins, pRB interacts with the cellular transcription factor E2F or a related Protein termed DRTF1. E2F associates with a form of pRB that is found primarily in G1 cells. It seems that the E2F-pRB complex dissociates near the G1-S boundary before the initiation of S phase, releasing free E2F and apparently stimulating the ability of E2F to activate transcription. Cells that express E1A have no or little pRB-E2F complex, presumably because of the association of E1A with pRB. During S phase, E2F forms a second complex that contains cyclin A but apparently lacks pRB. Here, we report that P107 is found in the cyclin A/E2F complex and that this complex also contains p33cdk2. These observations suggest that P107 and pRB cooperate in the regulation of E2F activity, each affecting different stages of the cell cycle. Thus, by binding to pRB and P107, E1A and large-T antigen target two distinct aspects of E2F regulation.
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independent binding of the retinoblastoma Protein and P107 to the transcription factor e2f
Nature, 1992Co-Authors: B Faha, Marlene Dembski, Lihuei Tsai, Ed Harlow, Nicholas J DysonAbstract:THE cellular Protein P107 and the retinoblastoma Protein (pRB) have many features in common. Most strikingly, they contain homologous Protein domains that mediate interaction with the oncoProteins of several small DNA tumour viruses, including adenovirus El A and SV40 large-T antigen1–9. In cells that do not contain these viral oncoProteins, pRB interacts with the cellular transcription factor E2F (refs 10–12) or a related Protein termed DRTF1 (ref. 13). E2F associates with a form of pRB that is found primarily in Gl cells10. It seems that the E2F-pRB complex dissociates near the Gl-S boundary before the initiation of S phase, releasing free E2F and apparently stimulating the ability of E2F to activate transcription14. Cells that express E1A have no or little pRB-E2F complex, presumably because of the association of E1A with pRB10–15. During S phase, E2F forms a second complex that contains cyclin A but apparently lacks pRB15. Here, we report that P107 is found in the cyclin A/E2F complex and that this complex also contains p33cdk2. These observations suggest that P107 and pRB cooperate in the regulation of E2F activity, each affecting different stages of the cell cycle. Thus, by binding to pRB and pi 07, El A and large-T antigen target two distinct aspects of E2F regulation.
John T. Minges - One of the best experts on this subject based on the ideXlab platform.
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proto oncogene activity of melanoma antigen a11 mage a11 regulates retinoblastoma related P107 and e2f1 Proteins
Journal of Biological Chemistry, 2013Co-Authors: Shifeng Su, John T. Minges, Amanda J. Blackwelder, Gail Grossman, James L Mohler, Elizabeth M WilsonAbstract:Melanoma antigen-A11 (MAGE-A11) is a low-abundance, primate-specific steroid receptor coregulator in normal tissues of the human reproductive tract that is expressed at higher levels in prostate cancer. Increased expression of MAGE-A11 enhances androgen receptor transcriptional activity and promotes prostate cancer cell growth. Further investigation into the mechanisms of MAGE-A11 function in prostate cancer demonstrated interactions with the retinoblastoma-related Protein P107 and Rb tumor suppressor but no interaction with p130 of the Rb family. MAGE-A11 interaction with P107 was associated with transcriptional repression in cells with low MAGE-A11 and transcriptional activation in cells with higher MAGE-A11. Selective interaction of MAGE-A11 with retinoblastoma family members suggested the regulation of E2F transcription factors. MAGE-A11 stabilized P107 by inhibition of ubiquitination and linked P107 to hypophosphorylated E2F1 in association with the stabilization and activation of E2F1. The androgen receptor and MAGE-A11 modulated endogenous expression of the E2F1-regulated cyclin-dependent kinase inhibitor p27Kip1. The ability of MAGE-A11 to increase E2F1 transcriptional activity was similar to the activity of adenovirus early oncoProtein E1A and depended on MAGE-A11 interactions with P107 and p300. The immunoreactivity of P107 and MAGE-A11 was greater in advanced prostate cancer than in benign prostate, and knockdown with small inhibitory RNA showed that P107 is a transcriptional activator in prostate cancer cells. These results suggest that MAGE-A11 is a proto-oncogene whose increased expression in prostate cancer reverses retinoblastoma-related Protein P107 from a transcriptional repressor to a transcriptional activator of the androgen receptor and E2F1.
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proto oncogene activity of melanoma antigen a11 mage a11 regulates retinoblastoma related P107 and e2f1 Proteins
Journal of Biological Chemistry, 2013Co-Authors: John T. Minges, Amanda J. Blackwelder, Gail Grossman, James L Mohler, Elizabeth M WilsonAbstract:Melanoma antigen-A11 (MAGE-A11) is a low-abundance, primate-specific steroid receptor coregulator in normal tissues of the human reproductive tract that is expressed at higher levels in prostate cancer. Increased expression of MAGE-A11 enhances androgen receptor transcriptional activity and promotes prostate cancer cell growth. Further investigation into the mechanisms of MAGE-A11 function in prostate cancer demonstrated interactions with the retinoblastoma-related Protein P107 and Rb tumor suppressor but no interaction with p130 of the Rb family. MAGE-A11 interaction with P107 was associated with transcriptional repression in cells with low MAGE-A11 and transcriptional activation in cells with higher MAGE-A11. Selective interaction of MAGE-A11 with retinoblastoma family members suggested the regulation of E2F transcription factors. MAGE-A11 stabilized P107 by inhibition of ubiquitination and linked P107 to hypophosphorylated E2F1 in association with the stabilization and activation of E2F1. The androgen receptor and MAGE-A11 modulated endogenous expression of the E2F1-regulated cyclin-dependent kinase inhibitor p27Kip1. The ability of MAGE-A11 to increase E2F1 transcriptional activity was similar to the activity of adenovirus early oncoProtein E1A and depended on MAGE-A11 interactions with P107 and p300. The immunoreactivity of P107 and MAGE-A11 was greater in advanced prostate cancer than in benign prostate, and knockdown with small inhibitory RNA showed that P107 is a transcriptional activator in prostate cancer cells. These results suggest that MAGE-A11 is a proto-oncogene whose increased expression in prostate cancer reverses retinoblastoma-related Protein P107 from a transcriptional repressor to a transcriptional activator of the androgen receptor and E2F1. Background: Primate-specific melanoma antigen-A11 (MAGE-A11) increases steroid receptor transcriptional activity and enhances prostate cancer cell growth. Results: MAGE-A11 activates E2F1 by interacting with retinoblastoma-related Protein P107. Conclusion: MAGE-A11 influences cell cycle regulatory pathways in a molecular hub for transcription. Significance: MAGE-A11 is a proto-oncogene whose increased expression impacts multiple signaling mechanisms that contribute to prostate cancer growth and progression.
