Abstract
We propose that the apoptotic function of p53 has an important role in B-cell homeostasis, which is important for the prevention of B-cell lymphomas. We created a mouse model (mΔpro) that lacked residues 58–88 of the proline-rich domain of p53. mΔpro is defective for apoptosis, but is able to arrest cell-cycle progression in hematopoietic tissues. mΔpro develops late-onset B-cell lymphoma, but not the thymic T-cell tumors found in p53-null mice. Interestingly, mΔpro lymphomas comprised incorrectly differentiated B cells. B-cell irregularities were also detected in mΔpro before tumor onset, in which aged mice showed an increased population of inappropriately differentiated B cells in the bone marrow and spleen. We predict that by keeping B-cell populations in check, p53-dependent apoptosis prevents irregular B cells from eventuating in lymphomas.
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Abbreviations
- BrdU:
-
bromo-deoxyuridine
- ES:
-
embryonic stem cells
- Δ, deletion, Pin1:
-
prolyl isomerise 1
- PCR:
-
polymerase chain reaction
- TP53 :
-
human p53 gene
- Trp53 :
-
mouse p53 gene
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Acknowledgements
We are grateful for technical assistance from N Bennett, J North, M Schultz, Z Lateef, B Li, X Tan, and L Wallis. L Hananeia and S Edwards are acknowledged for their contributions to the early phases of this study. I Morison, D Speidel, and H Campbell are thanked for comments on the paper. This work was supported by a grant from the Royal Society of New Zealand Marsden Fund, a Cancer Institute NSW Program Grant, and a Health Research Council of New Zealand project grant.
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Slatter, T., Ganesan, P., Holzhauer, C. et al. p53-mediated apoptosis prevents the accumulation of progenitor B cells and B-cell tumors. Cell Death Differ 17, 540–550 (2010). https://doi.org/10.1038/cdd.2009.136
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DOI: https://doi.org/10.1038/cdd.2009.136
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