A role for E2F1 in the induction of ARF, p53, and apoptosis during thymic negative selection.
E2F transcriptional activity controls the expression of many of the genes required for G1 to S phase progression. E2F1, one member of the E2F family, plays an important role in the induction of apoptosis. We have examined the role of the E2F1 transcription factor in apoptosis during T-cell maturation in the thymus. We show that E2F1 is required for the apoptosis of autoimmune immature T cells during thymic negative selection in vivo. This T-cell receptor-mediated apoptosis coincides with the E2F1-dependent increase of p19-ARF mRNA and p53 protein levels. In contrast, E2F1 is not required for the induction of apoptosis by glucocorticoids or DNA damage. These results demonstrate a specific role for E2F1, which triggers a pathway leading to ARF and p53 induction, in a physiological apoptosis pathway that is uncoupled from a normal proliferative event.
Zhu
J W
JW
Department of Biochemistry, University of Colorado Health Sciences Center, Denver 80262, USA.
DeRyckere
D
D
Li
F X
FX
Wan
Y Y
YY
DeGregori
J
J
D000818:Animals; D000956:Antigens, Viral / Q000276:immunology; D017209:Apoptosis; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D004249:DNA Damage; D004268:DNA-Binding Proteins; D003907:Dexamethasone / Q000494:pharmacology; D004317:Doxorubicin / Q000494:pharmacology; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D014176:Protein Biosynthesis; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D056465:Retinoblastoma-Binding Protein 1; D012190:Retroviridae / Q000276:immunology; D018089:Superantigens / Q000276:immunology; D013950:Thymus Gland / Q000166:cytology*; D050680:Transcription Factor DP1; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D025803:Tumor Suppressor Protein p14ARF; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis*
D000956:Antigens, Viral; C533431:Arid4a protein, mouse; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; C493754:E2f1 protein, mouse; D011948:Receptors, Antigen, T-Cell; D056465:Retinoblastoma-Binding Protein 1; D018089:Superantigens; D050680:Transcription Factor DP1; D014157:Transcription Factors; D025803:Tumor Suppressor Protein p14ARF; D016159:Tumor Suppressor Protein p53; D003907:Dexamethasone; D004317:Doxorubicin