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53BP1 and USP28 mediate p53-dependent cell cycle arrest in response to centrosome loss and prolonged mitosis

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Summary

This article examines the role of 53BP1 and USP28 in mediating p53-dependent cell cycle arrest in response to centrosome loss and prolonged mitosis. Results from CRISPR-mediated loss-of-function screens and further experiments indicate that 53BP1 mediates p53 activation independently of its DNA repair activity, while USP28 can directly deubiquitinate p53 and stabilize it. The findings suggest that the 53BP1 and USP28 pathway acts in parallel to the spindle assembly checkpoint to select against disturbed or delayed mitosis, promoting mitotic efficiency.

Q&As

What proteins were identified as essential for p53-dependent cell cycle arrest in response to centrosome loss and prolonged mitosis?
53BP1 and USP28 were identified as essential for p53-dependent cell cycle arrest in response to centrosome loss and prolonged mitosis.

How is 53BP1 involved in p53 activation independently of its DNA repair activity?
53BP1 mediates p53 activation independently of its DNA repair activity by requiring its interacting protein USP28, which can directly deubiquitinate p53 in vitro and ectopically stabilize p53 in vivo.

How does the spindle assembly checkpoint protect mitotic accuracy?
The spindle assembly checkpoint protects mitotic accuracy by slowing down mitosis.

Is DDR function intact in 53BP1 WT, 53BP1 ΔBRCT, and 53BP1 ΔBRCT PIPBOX mutants?
Yes, DDR function is intact in 53BP1 WT, 53BP1 ΔBRCT, and 53BP1 ΔBRCT PIPBOX mutants.

What role does USP28 play in p53 stabilization during centrosome loss-induced G1 arrest?
USP28 is catalytically required for p53 stabilization during centrosome loss-induced G1 arrest.

AI Comments

👍 This article provides an in-depth and well-researched analysis of the role of 53BP1 and USP28 in p53-dependent cell cycle arrest in response to centrosome loss and prolonged mitosis.

👎 This article fails to address the potential implications of the findings on other cell cycle processes.

AI Discussion

Me: The article discusses how 53BP1 and USP28 can mediate p53-dependent cell cycle arrest in response to centrosome loss and prolonged mitosis. It suggests that while the spindle assembly checkpoint (SAC) protects mitotic accuracy, 53BP1 and USP28 can select against disturbed or delayed mitosis to promote mitotic efficiency.

Friend: That's really interesting. What are the implications of this research?

Me: This research suggests that 53BP1 and USP28 could be used to help regulate cell cycle and prevent errors in mitosis. This could have implications for treating cancer, as it suggests that these proteins could be used to target cancer cells and prevent them from dividing and spreading. It could also be useful in the development of new drugs that target the cell cycle and prevent the growth and spread of cancer.

Action items

Research the role of 53BP1 and USP28 in p53-dependent cell cycle arrest in response to centrosome loss and prolonged mitosis.
Explore the potential of using CRISPR-mediated loss-of-function screens to identify components required for centrosome loss-induced G1 arrest.
Investigate the mechanism of how 53BP1 and USP28 function in parallel to select against disturbed or delayed mitosis, promoting mitotic efficiency.

Technical terms

53BP1: Tumor Suppressor p53-Binding Protein 1, a protein that binds to the tumor suppressor protein p53 and is involved in DNA repair.
USP28: Ubiquitin Thiolesterase, an enzyme that can deubiquitinate p53 and stabilize it.
p53: Tumor Suppressor Protein p53, a transcription factor that is involved in cell cycle arrest and apoptosis.
p21: CDKN1A protein, a cyclin-dependent kinase inhibitor that is involved in cell cycle arrest.
Centrosome: A cellular organelle that is involved in the formation of the mitotic spindle during cell division.
Mitosis: The process of cell division in which a single cell divides into two daughter cells.