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Cancer Biology Commons

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Full-Text Articles in Cancer Biology

Phosphorylation Of The Mdm2 Oncoprotein By The C-Abl Tyrosine Kinase Regulates P53 Tumor Suppression And The Radiosensitivity Of Mice, Michael I. Carr, Justine E. Roderick, Hong Zhang, Bruce A. Woda, Michelle A. Kelliher, Stephen N. Jones Dec 2016

Phosphorylation Of The Mdm2 Oncoprotein By The C-Abl Tyrosine Kinase Regulates P53 Tumor Suppression And The Radiosensitivity Of Mice, Michael I. Carr, Justine E. Roderick, Hong Zhang, Bruce A. Woda, Michelle A. Kelliher, Stephen N. Jones

UMass Metabolic Network Publications

The p53 tumor suppressor acts as a guardian of the genome by preventing the propagation of DNA damage-induced breaks and mutations to subsequent generations of cells. We have previously shown that phosphorylation of the Mdm2 oncoprotein at Ser394 by the ATM kinase is required for robust p53 stabilization and activation in cells treated with ionizing radiation, and that loss of Mdm2 Ser394 phosphorylation leads to spontaneous tumorigenesis and radioresistance in Mdm2S394A mice. Previous in vitro data indicate that the c-Abl kinase phosphorylates Mdm2 at the neighboring residue (Tyr393) in response to DNA damage to regulate p53-dependent apoptosis. In this present ...


F-Box Protein Fbxo31 Directs Degradation Of Mdm2 To Facilitate P53-Mediated Growth Arrest Following Genotoxic Stress, Sunil K. Malonia, Parul Dutta, Manas Kumar Santra, Michael R. Green Jul 2015

F-Box Protein Fbxo31 Directs Degradation Of Mdm2 To Facilitate P53-Mediated Growth Arrest Following Genotoxic Stress, Sunil K. Malonia, Parul Dutta, Manas Kumar Santra, Michael R. Green

Molecular, Cell and Cancer Biology Publications

The tumor suppressor p53 plays a critical role in maintaining genomic stability. In response to genotoxic stress, p53 levels increase and induce cell-cycle arrest, senescence, or apoptosis, thereby preventing replication of damaged DNA. In unstressed cells, p53 is maintained at a low level. The major negative regulator of p53 is MDM2, an E3 ubiquitin ligase that directly interacts with p53 and promotes its polyubiquitination, leading to the subsequent destruction of p53 by the 26S proteasome. Following DNA damage, MDM2 is degraded rapidly, resulting in increased p53 stability. Because of the important role of MDM2 in modulating p53 function, it is ...


Defining The Roles Of P300/Cbp (Creb Binding Protein) And S5a In P53 Polyubiquitination, Degradation And Dna Damage Responses: A Dissertation, Dingding Shi Jan 2010

Defining The Roles Of P300/Cbp (Creb Binding Protein) And S5a In P53 Polyubiquitination, Degradation And Dna Damage Responses: A Dissertation, Dingding Shi

GSBS Dissertations and Theses

p53, known as the “guardian of the genome”, is the most well-characterized tumor suppressor gene. The central role of p53 is to prevent genome instability. p53 is the central node in an incredibly elaborate genome defense network for receiving various input stress signals and controlling diverse cellular responses. The final output of this network is determined not only by the p53 protein itself, but also by other p53 cooperating proteins.

p300 and CBP (CREB-Binding Protein) act as multifunctional regulators of p53 via acetylase and ubiquitin ligase activities. Prior work in vitro has shown that the N-terminal 595 aa of p300 ...