Increased T-cell apoptosis and terminal B-cell differentiation induced by inactivation of the Ets-1 proto-oncogene.
The Ets-1 proto-oncogene is a member of a transcription factor family characterized by homology to the v-ets oncogene. In adult mice, Ets-1 is expressed predominantly in lymphoid cells where it has been implicated in regulating transcription of lymphocyte-specific genes. Following T-cell activation, the specific DNA binding activity of Ets-1 is inactivated by transient phosphorylation, suggesting a function in the transition from the resting to activated state. Ets-1 has also been suggested to cooperate with the AP-1 transcription factor complex to mediate cellular growth factor responses. Here we show, by using RAG-2-deficient blastocyst complementation, that Ets-1 deficiency has dramatic, but different, effects on development and function of T- and B-lineage cells. Ets-1-deficient T cells were present in reduced numbers and were highly susceptible to cell death in vitro. In contrast, Ets-1-deficient B cells were present in normal numbers but a large proportion were IgM plasma cells. Our data demonstrate that Ets-1 is essential for maintenance of the normal pool of resting T- and B-lineage cells.
Bories
J C
JC
Howard Hughes Medical Institute, Children's Hospital, Boston, Massachusetts 02115, USA.
Willerford
D M
DM
Grévin
D
D
Davidson
L
L
Camus
A
A
Martin
P
P
Stéhelin
D
D
Alt
F W
FW
D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000502:physiology*; D001402:B-Lymphocytes / Q000166:cytology / Q000502:physiology*; D001755:Blastocyst / Q000166:cytology; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology*; D002460:Cell Line; D002678:Chimera; D004268:DNA-Binding Proteins; D051379:Mice; D011506:Proteins / Q000502:physiology; D000090063:Proto-Oncogene Mas; D050784:Proto-Oncogene Protein c-ets-1; D011518:Proto-Oncogene Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D050783:Proto-Oncogene Proteins c-ets; D011519:Proto-Oncogenes; D013154:Spleen / Q000166:cytology; D013234:Stem Cells; D013601:T-Lymphocytes / Q000502:physiology*; D014157:Transcription Factors / Q000172:deficiency / Q000235:genetics / Q000502:physiology*
D004268:DNA-Binding Proteins; C494041:ETS1 protein, human; C494042:Ets1 protein, mouse; C000715470:MAS1 protein, human; D011506:Proteins; D000090063:Proto-Oncogene Mas; D050784:Proto-Oncogene Protein c-ets-1; D011518:Proto-Oncogene Proteins; D050783:Proto-Oncogene Proteins c-ets; C499308:Rag2 protein, mouse; D014157:Transcription Factors; C064655:V(D)J recombination activating protein 2