p53-mediated apoptosis prevents the accumulation of progenitor B cells and B-cell tumors.
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.
Department of Pathology, School of Medicine, University of Otago, Dunedin, New Zealand.
T L
TL
Slatter
P
P
Ganesan
C
C
Holzhauer
R
R
Mehta
C
C
Rubio
G
G
Williams
M
M
Wilson
J A
JA
Royds
M A
MA
Baird
A W
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Braithwaite
D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D001854:Bone Marrow Cells / Q000166:cytology / Q000502:physiology; D002453:Cell Cycle / Q000502:physiology; D002454:Cell Differentiation; D004249:DNA Damage; D005786:Gene Expression Regulation; D006706:Homeostasis; D016393:Lymphoma, B-Cell / Q000517:prevention & control*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D054448:Precursor Cells, B-Lymphoid / Q000166:cytology / Q000502:physiology*; D015996:Survival Rate; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
D016159:Tumor Suppressor Protein p53