p53-mediated apoptosis prevents the accumulation of progenitor B cells and B-cell tumors
| Autor: | Margaret A. Baird, P Ganesan, Antony W. Braithwaite, C Rubio, Michelle Wilson, Reena Mehta, C Holzhauer, Tania L. Slatter, Janice A. Royds, Gail Williams |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
Pathology
medicine.medical_specialty Lymphoma B-Cell Molecular Sequence Data Population Apoptosis Bone Marrow Cells Spleen Biology Mice medicine Animals Homeostasis Amino Acid Sequence education Molecular Biology B cell Mice Knockout education.field_of_study Precursor Cells B-Lymphoid Cell Cycle Hematopoietic Tissue Cell Differentiation Cell Biology medicine.disease Lymphoma Mice Inbred C57BL Survival Rate medicine.anatomical_structure Gene Expression Regulation Cancer research Bone marrow Tumor Suppressor Protein p53 DNA Damage |
| Zdroj: | Cell Death & Differentiation. 17:540-550 |
| ISSN: | 1476-5403 1350-9047 |
| DOI: | 10.1038/cdd.2009.136 |
| Popis: | 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 (mDeltapro) that lacked residues 58-88 of the proline-rich domain of p53. mDeltapro is defective for apoptosis, but is able to arrest cell-cycle progression in hematopoietic tissues. mDeltapro develops late-onset B-cell lymphoma, but not the thymic T-cell tumors found in p53-null mice. Interestingly, mDeltapro lymphomas comprised incorrectly differentiated B cells. B-cell irregularities were also detected in mDeltapro 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. |
| Databáze: | OpenAIRE |
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