Id3 induces growth arrest and caspase-2-dependent apoptosis in B lymphocyte progenitors.
The E-protein transcription factors E2A, HEB, and E2-2 play an essential role in the differentiation, proliferation, and survival of B lymphocyte progenitors (BLPs). In this study, we show that the E-protein antagonist Id3 induces apoptosis of both primary and transformed BLPs through a caspase-2-dependent mechanism that does not require p53 and is not inhibited by bcl-2. Id3 expressing B lineage cells show reduced expression of known E-protein target genes as well as multiple genes involved in cell proliferation. We hypothesize that Id3 induces activation of caspase-2 as a consequence of severe or "catastrophic" growth arrest. In support of this hypothesis, we show that chemical-induced growth arrest is sufficient to activate caspase-2 and induce apoptosis in BLPs. Our data suggest that E-proteins function in the control of differentiation and proliferation and that diminished E-protein activity results in apoptosis as a consequence of growth arrest.
Kee
Barbara L
BL
Department of Pathology, University of Chicago, Chicago, IL 60637, USA. bkee@bsd.uchicago.edu
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D001402:B-Lymphocytes / Q000166:cytology / Q000502:physiology*; D053143:Caspase 2; D053148:Caspase 3; D053453:Caspase 9; D020169:Caspases / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology; D049109:Cell Proliferation; D002478:Cells, Cultured; D006224:Cricetinae; D003546:Cysteine Endopeptidases / Q000502:physiology*; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000502:physiology*; D051796:Inhibitor of Differentiation Proteins / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000502:physiology; D016159:Tumor Suppressor Protein p53 / Q000172:deficiency / Q000235:genetics
D051796:Inhibitor of Differentiation Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; C067679:Idb3 protein, mouse; C090208:Casp2 protein, mouse; C505409:Casp3 protein, mouse; C506434:Casp9 protein, mouse; D053143:Caspase 2; D053148:Caspase 3; D053453:Caspase 9; D020169:Caspases; D003546:Cysteine Endopeptidases