Involvement of 53BP1, a p53 Binding Protein, in Chk2 Phosphorylation of p53 and DNA Damage Cell Cycle Checkpoints

2004 ◽  
Author(s):  
Bin Wang ◽  
Stephan Elledge
Keyword(s):  
Cell Cycle ◽  
Dna Damage ◽  
Binding Protein ◽  
Cell Cycle Checkpoints ◽  
Damage Cell

scholarly journals Targeting the p53 Pathway in Ewing Sarcoma

Sarcoma ◽  
2011 ◽  
Vol 2011 ◽  
pp. 1-17 ◽  
Author(s):  
Paul M. Neilsen ◽  
Kathleen I. Pishas ◽  
David F. Callen ◽  
David M. Thomas
Keyword(s):  
Cell Cycle ◽  
Dna Damage ◽  
Ewing Sarcoma ◽  
Gene Rearrangement ◽  
Cell Cycle Checkpoints ◽  
Wild Type ◽  
Damage Cell ◽  
Downstream Signaling ◽  
Functional Capabilities ◽  
Wild Type P53

The p53 tumour suppressor plays a pivotal role in the prevention of oncogenic transformation. Cancers frequently evade the potent antitumour surveillance mechanisms of p53 through mutation of theTP53gene, with approximately 50% of all human malignancies expressing dysfunctional, mutated p53 proteins. Interestingly, genetic lesions in theTP53gene are only observed in 10% of Ewing Sarcomas, with the majority of these sarcomas expressing a functional wild-type p53. In addition, the p53 downstream signaling pathways and DNA-damage cell cycle checkpoints remain functionally intact in these sarcomas. This paper summarizes recent insights into the functional capabilities and regulation of p53 in Ewing Sarcoma, with a particular focus on the cross-talk between p53 and the EWS-FLI1 gene rearrangement frequently associated with this disease. The development of several activators of p53 is discussed, with recent evidence demonstrating the potential of small molecule p53 activators as a promising systemic therapeutic approach for the treatment of Ewing Sarcomas with wild-type p53.

scholarly journals The transcription factors TFE3 and TFEB amplify p53 dependent transcriptional programs in response to DNA damage

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Eutteum Jeong ◽  
Owen A Brady ◽  
José A Martina ◽  
Mehdi Pirooznia ◽  
Ilker Tunc ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Dna Damage ◽  
Transcription Factors ◽  
P53 Protein ◽  
Cell Cycle Control ◽  
Cell Cycle Checkpoints ◽  
Dependent Manner ◽  
Double Knockout ◽  
Protein Levels ◽  
Regulation Of Cell Cycle

The transcription factors TFE3 and TFEB cooperate to regulate autophagy induction and lysosome biogenesis in response to starvation. Here we demonstrate that DNA damage activates TFE3 and TFEB in a p53 and mTORC1 dependent manner. RNA-Seq analysis of TFEB/TFE3 double-knockout cells exposed to etoposide reveals a profound dysregulation of the DNA damage response, including upstream regulators and downstream p53 targets. TFE3 and TFEB contribute to sustain p53-dependent response by stabilizing p53 protein levels. In TFEB/TFE3 DKOs, p53 half-life is significantly decreased due to elevated Mdm2 levels. Transcriptional profiles of genes involved in lysosome membrane permeabilization and cell death pathways are dysregulated in TFEB/TFE3-depleted cells. Consequently, prolonged DNA damage results in impaired LMP and apoptosis induction. Finally, expression of multiple genes implicated in cell cycle control is altered in TFEB/TFE3 DKOs, revealing a previously unrecognized role of TFEB and TFE3 in the regulation of cell cycle checkpoints in response to stress.

Cr(VI) Induces DNA Damage, Cell Cycle Arrest and Polyploidization: A Flow Cytometric and Comet Assay Study inPisum sativum

2011 ◽  
Vol 24 (7) ◽  
pp. 1040-1047 ◽  
Author(s):  
Eleazar Rodriguez ◽  
Raquel Azevedo ◽  
Pedro Fernandes ◽  
Conceic¸ão Santos
Keyword(s):  
Cell Cycle ◽  
Dna Damage ◽  
Comet Assay ◽  
Cell Cycle Arrest ◽  
Damage Cell ◽  
Cycle Arrest ◽  
Flow Cytometric
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