Mdm2 promotes Cdc25C protein degradation and delays cell cycle progression through the G2/M phase
Upon different types of stress, the gene encoding the mitosis-promoting phosphatase Cdc25C is transcriptionally repressed by p53, contributing to p53’s enforcement of a G2 cell cycle arrest. In addition, Cdc25C protein stability is also decreased following DNA damage. Mdm2, another p53 target gene,...
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todo:paper_09509232_v36_n49_p6762_Giono2023-10-03T15:50:31Z Mdm2 promotes Cdc25C protein degradation and delays cell cycle progression through the G2/M phase Giono, L.E. Resnick-Silverman, L. Carvajal, L.A. St Clair, S. Manfredi, J.J. Cdc25C protein proteasome protein MDM2 protein p53 protein tyrosine phosphatase small interfering RNA ubiquitin protein ligase unclassified drug antineoplastic antibiotic doxorubicin MDM2 protein, human protein MDM2 protein p53 protein tyrosine phosphatase animal cell Article Cdc25C gene controlled study DNA damage down regulation embryo enzyme metabolism enzyme stability G2 phase cell cycle checkpoint gene amplification gene expression regulation gene interaction gene knockdown gene overexpression gene repression human Mdm2 gene mouse nonhuman oncogene priority journal promoter region protein degradation protein expression protein function protein protein interaction protein targeting transcription regulation tumor suppressor gene ubiquitination animal cell culture cell line drug effects G2 phase cell cycle checkpoint genetics HCT 116 cell line immunoblotting knockout mouse metabolism protein degradation RNA interference tumor cell line Animals Antibiotics, Antineoplastic cdc25 Phosphatases Cell Line Cell Line, Tumor Cells, Cultured Down-Regulation Doxorubicin G2 Phase Cell Cycle Checkpoints Gene Expression Regulation HCT116 Cells Humans Immunoblotting Mice, Knockout Proteolysis Proto-Oncogene Proteins c-mdm2 RNA Interference Tumor Suppressor Protein p53 Upon different types of stress, the gene encoding the mitosis-promoting phosphatase Cdc25C is transcriptionally repressed by p53, contributing to p53’s enforcement of a G2 cell cycle arrest. In addition, Cdc25C protein stability is also decreased following DNA damage. Mdm2, another p53 target gene, encodes a ubiquitin ligase that negatively regulates p53 levels by ubiquitination. Ablation of Mdm2 by siRNA led to an increase in p53 protein and repression of Cdc25C gene expression. However, Cdc25C protein levels were actually increased following Mdm2 depletion. Mdm2 is shown to negatively regulate Cdc25C protein levels by reducing its half-life independently of the presence of p53. Further, Mdm2 physically interacts with Cdc25C and promotes its degradation through the proteasome in a ubiquitin-independent manner. Either Mdm2 overexpression or Cdc25C downregulation delays cell cycle progression through the G2/M phase. Thus, the repression of the Cdc25C promoter by p53, together with p53-dependent induction of Mdm2 and subsequent degradation of Cdc25C, could provide a dual mechanism by which p53 can enforce and maintain a G2/M cell cycle arrest. © 2017 Macmillan Publishers Limited, part of Springer Nature. All rights reserved. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_09509232_v36_n49_p6762_Giono |
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Universidad de Buenos Aires |
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I-28 |
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R-134 |
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Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
Cdc25C protein proteasome protein MDM2 protein p53 protein tyrosine phosphatase small interfering RNA ubiquitin protein ligase unclassified drug antineoplastic antibiotic doxorubicin MDM2 protein, human protein MDM2 protein p53 protein tyrosine phosphatase animal cell Article Cdc25C gene controlled study DNA damage down regulation embryo enzyme metabolism enzyme stability G2 phase cell cycle checkpoint gene amplification gene expression regulation gene interaction gene knockdown gene overexpression gene repression human Mdm2 gene mouse nonhuman oncogene priority journal promoter region protein degradation protein expression protein function protein protein interaction protein targeting transcription regulation tumor suppressor gene ubiquitination animal cell culture cell line drug effects G2 phase cell cycle checkpoint genetics HCT 116 cell line immunoblotting knockout mouse metabolism protein degradation RNA interference tumor cell line Animals Antibiotics, Antineoplastic cdc25 Phosphatases Cell Line Cell Line, Tumor Cells, Cultured Down-Regulation Doxorubicin G2 Phase Cell Cycle Checkpoints Gene Expression Regulation HCT116 Cells Humans Immunoblotting Mice, Knockout Proteolysis Proto-Oncogene Proteins c-mdm2 RNA Interference Tumor Suppressor Protein p53 |
| spellingShingle |
Cdc25C protein proteasome protein MDM2 protein p53 protein tyrosine phosphatase small interfering RNA ubiquitin protein ligase unclassified drug antineoplastic antibiotic doxorubicin MDM2 protein, human protein MDM2 protein p53 protein tyrosine phosphatase animal cell Article Cdc25C gene controlled study DNA damage down regulation embryo enzyme metabolism enzyme stability G2 phase cell cycle checkpoint gene amplification gene expression regulation gene interaction gene knockdown gene overexpression gene repression human Mdm2 gene mouse nonhuman oncogene priority journal promoter region protein degradation protein expression protein function protein protein interaction protein targeting transcription regulation tumor suppressor gene ubiquitination animal cell culture cell line drug effects G2 phase cell cycle checkpoint genetics HCT 116 cell line immunoblotting knockout mouse metabolism protein degradation RNA interference tumor cell line Animals Antibiotics, Antineoplastic cdc25 Phosphatases Cell Line Cell Line, Tumor Cells, Cultured Down-Regulation Doxorubicin G2 Phase Cell Cycle Checkpoints Gene Expression Regulation HCT116 Cells Humans Immunoblotting Mice, Knockout Proteolysis Proto-Oncogene Proteins c-mdm2 RNA Interference Tumor Suppressor Protein p53 Giono, L.E. Resnick-Silverman, L. Carvajal, L.A. St Clair, S. Manfredi, J.J. Mdm2 promotes Cdc25C protein degradation and delays cell cycle progression through the G2/M phase |
| topic_facet |
Cdc25C protein proteasome protein MDM2 protein p53 protein tyrosine phosphatase small interfering RNA ubiquitin protein ligase unclassified drug antineoplastic antibiotic doxorubicin MDM2 protein, human protein MDM2 protein p53 protein tyrosine phosphatase animal cell Article Cdc25C gene controlled study DNA damage down regulation embryo enzyme metabolism enzyme stability G2 phase cell cycle checkpoint gene amplification gene expression regulation gene interaction gene knockdown gene overexpression gene repression human Mdm2 gene mouse nonhuman oncogene priority journal promoter region protein degradation protein expression protein function protein protein interaction protein targeting transcription regulation tumor suppressor gene ubiquitination animal cell culture cell line drug effects G2 phase cell cycle checkpoint genetics HCT 116 cell line immunoblotting knockout mouse metabolism protein degradation RNA interference tumor cell line Animals Antibiotics, Antineoplastic cdc25 Phosphatases Cell Line Cell Line, Tumor Cells, Cultured Down-Regulation Doxorubicin G2 Phase Cell Cycle Checkpoints Gene Expression Regulation HCT116 Cells Humans Immunoblotting Mice, Knockout Proteolysis Proto-Oncogene Proteins c-mdm2 RNA Interference Tumor Suppressor Protein p53 |
| description |
Upon different types of stress, the gene encoding the mitosis-promoting phosphatase Cdc25C is transcriptionally repressed by p53, contributing to p53’s enforcement of a G2 cell cycle arrest. In addition, Cdc25C protein stability is also decreased following DNA damage. Mdm2, another p53 target gene, encodes a ubiquitin ligase that negatively regulates p53 levels by ubiquitination. Ablation of Mdm2 by siRNA led to an increase in p53 protein and repression of Cdc25C gene expression. However, Cdc25C protein levels were actually increased following Mdm2 depletion. Mdm2 is shown to negatively regulate Cdc25C protein levels by reducing its half-life independently of the presence of p53. Further, Mdm2 physically interacts with Cdc25C and promotes its degradation through the proteasome in a ubiquitin-independent manner. Either Mdm2 overexpression or Cdc25C downregulation delays cell cycle progression through the G2/M phase. Thus, the repression of the Cdc25C promoter by p53, together with p53-dependent induction of Mdm2 and subsequent degradation of Cdc25C, could provide a dual mechanism by which p53 can enforce and maintain a G2/M cell cycle arrest. © 2017 Macmillan Publishers Limited, part of Springer Nature. All rights reserved. |
| format |
JOUR |
| author |
Giono, L.E. Resnick-Silverman, L. Carvajal, L.A. St Clair, S. Manfredi, J.J. |
| author_facet |
Giono, L.E. Resnick-Silverman, L. Carvajal, L.A. St Clair, S. Manfredi, J.J. |
| author_sort |
Giono, L.E. |
| title |
Mdm2 promotes Cdc25C protein degradation and delays cell cycle progression through the G2/M phase |
| title_short |
Mdm2 promotes Cdc25C protein degradation and delays cell cycle progression through the G2/M phase |
| title_full |
Mdm2 promotes Cdc25C protein degradation and delays cell cycle progression through the G2/M phase |
| title_fullStr |
Mdm2 promotes Cdc25C protein degradation and delays cell cycle progression through the G2/M phase |
| title_full_unstemmed |
Mdm2 promotes Cdc25C protein degradation and delays cell cycle progression through the G2/M phase |
| title_sort |
mdm2 promotes cdc25c protein degradation and delays cell cycle progression through the g2/m phase |
| url |
http://hdl.handle.net/20.500.12110/paper_09509232_v36_n49_p6762_Giono |
| work_keys_str_mv |
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