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Myc stimulates cell cycle progression through the activation of Cdk1 and phosphorylation of p27
by
Sicinski, Piotr
, Fernández, Adrián
, Blanco, Rosa
, Santamaría, David
, Bretones, Gabriel
, León, Javier
, García-Gutiérrez, Lucía
, Symonds, Catherine
, Alonso, Leticia
, Molina, Ester
, Arechaga, Ignacio
, Acosta, Juan C.
, Barbacid, Mariano
in
631/337
/ 631/67
/ 631/80
/ Animals
/ CDC2 Protein Kinase - metabolism
/ CDC2 Protein Kinase - physiology
/ Cell Cycle
/ Cell Cycle Checkpoints
/ Cell Cycle Proteins - metabolism
/ Cell Division
/ Cell Line
/ Cyclin-Dependent Kinase 2
/ Cyclin-Dependent Kinase 4 - metabolism
/ Cyclin-Dependent Kinase Inhibitor p15 - metabolism
/ Cyclin-Dependent Kinase Inhibitor p21 - metabolism
/ Cyclin-Dependent Kinase Inhibitor p27 - metabolism
/ Cyclin-Dependent Kinase Inhibitor p27 - physiology
/ Cyclin-Dependent Kinases - metabolism
/ Cyclins - metabolism
/ Female
/ HEK293 Cells
/ HeLa Cells
/ Humanities and Social Sciences
/ Humans
/ Male
/ Mice
/ Mice, Inbred C57BL
/ multidisciplinary
/ Myc protein
/ Phosphorylation
/ Proto-Oncogene Proteins c-myc - metabolism
/ Proto-Oncogene Proteins c-myc - physiology
/ Science
/ Science (multidisciplinary)
/ Signal Transduction
2019
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Myc stimulates cell cycle progression through the activation of Cdk1 and phosphorylation of p27
by
Sicinski, Piotr
, Fernández, Adrián
, Blanco, Rosa
, Santamaría, David
, Bretones, Gabriel
, León, Javier
, García-Gutiérrez, Lucía
, Symonds, Catherine
, Alonso, Leticia
, Molina, Ester
, Arechaga, Ignacio
, Acosta, Juan C.
, Barbacid, Mariano
in
631/337
/ 631/67
/ 631/80
/ Animals
/ CDC2 Protein Kinase - metabolism
/ CDC2 Protein Kinase - physiology
/ Cell Cycle
/ Cell Cycle Checkpoints
/ Cell Cycle Proteins - metabolism
/ Cell Division
/ Cell Line
/ Cyclin-Dependent Kinase 2
/ Cyclin-Dependent Kinase 4 - metabolism
/ Cyclin-Dependent Kinase Inhibitor p15 - metabolism
/ Cyclin-Dependent Kinase Inhibitor p21 - metabolism
/ Cyclin-Dependent Kinase Inhibitor p27 - metabolism
/ Cyclin-Dependent Kinase Inhibitor p27 - physiology
/ Cyclin-Dependent Kinases - metabolism
/ Cyclins - metabolism
/ Female
/ HEK293 Cells
/ HeLa Cells
/ Humanities and Social Sciences
/ Humans
/ Male
/ Mice
/ Mice, Inbred C57BL
/ multidisciplinary
/ Myc protein
/ Phosphorylation
/ Proto-Oncogene Proteins c-myc - metabolism
/ Proto-Oncogene Proteins c-myc - physiology
/ Science
/ Science (multidisciplinary)
/ Signal Transduction
2019
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Myc stimulates cell cycle progression through the activation of Cdk1 and phosphorylation of p27
by
Sicinski, Piotr
, Fernández, Adrián
, Blanco, Rosa
, Santamaría, David
, Bretones, Gabriel
, León, Javier
, García-Gutiérrez, Lucía
, Symonds, Catherine
, Alonso, Leticia
, Molina, Ester
, Arechaga, Ignacio
, Acosta, Juan C.
, Barbacid, Mariano
in
631/337
/ 631/67
/ 631/80
/ Animals
/ CDC2 Protein Kinase - metabolism
/ CDC2 Protein Kinase - physiology
/ Cell Cycle
/ Cell Cycle Checkpoints
/ Cell Cycle Proteins - metabolism
/ Cell Division
/ Cell Line
/ Cyclin-Dependent Kinase 2
/ Cyclin-Dependent Kinase 4 - metabolism
/ Cyclin-Dependent Kinase Inhibitor p15 - metabolism
/ Cyclin-Dependent Kinase Inhibitor p21 - metabolism
/ Cyclin-Dependent Kinase Inhibitor p27 - metabolism
/ Cyclin-Dependent Kinase Inhibitor p27 - physiology
/ Cyclin-Dependent Kinases - metabolism
/ Cyclins - metabolism
/ Female
/ HEK293 Cells
/ HeLa Cells
/ Humanities and Social Sciences
/ Humans
/ Male
/ Mice
/ Mice, Inbred C57BL
/ multidisciplinary
/ Myc protein
/ Phosphorylation
/ Proto-Oncogene Proteins c-myc - metabolism
/ Proto-Oncogene Proteins c-myc - physiology
/ Science
/ Science (multidisciplinary)
/ Signal Transduction
2019
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Myc stimulates cell cycle progression through the activation of Cdk1 and phosphorylation of p27
Journal Article
Myc stimulates cell cycle progression through the activation of Cdk1 and phosphorylation of p27
2019
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Overview
Cell cycle stimulation is a major transforming mechanism of Myc oncoprotein. This is achieved through at least three concomitant mechanisms: upregulation of cyclins and Cdks, downregulation of the Cdk inhibitors p15 and p21 and the degradation of p27. The Myc-p27 antagonism has been shown to be relevant in human cancer. To be degraded, p27 must be phosphorylated at Thr-187 to be recognized by Skp2, a component of the ubiquitination complex. We previously described that Myc induces Skp2 expression. Here we show that not only Cdk2 but Cdk1 phosphorylates p27 at the Thr-187. Moreover, Myc induced p27 degradation in murine fibroblasts through Cdk1 activation, which was achieved by Myc-dependent cyclin A and B induction. In the absence of Cdk2, p27 phosphorylation at Thr-187 was mainly carried out by cyclin A2-Cdk1 and cyclin B1-Cdk1. We also show that Cdk1 inhibition was enough for the synthetic lethal interaction with Myc. This result is relevant because Cdk1 is the only Cdk strictly required for cell cycle and the reported synthetic lethal interaction between Cdk1 and Myc.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ 631/67
/ 631/80
/ Animals
/ CDC2 Protein Kinase - metabolism
/ CDC2 Protein Kinase - physiology
/ Cell Cycle Proteins - metabolism
/ Cyclin-Dependent Kinase 4 - metabolism
/ Cyclin-Dependent Kinase Inhibitor p15 - metabolism
/ Cyclin-Dependent Kinase Inhibitor p21 - metabolism
/ Cyclin-Dependent Kinase Inhibitor p27 - metabolism
/ Cyclin-Dependent Kinase Inhibitor p27 - physiology
/ Cyclin-Dependent Kinases - metabolism
/ Female
/ Humanities and Social Sciences
/ Humans
/ Male
/ Mice
/ Proto-Oncogene Proteins c-myc - metabolism
/ Proto-Oncogene Proteins c-myc - physiology
/ Science
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