Apoptotic signals delivered through the T-cell receptor of a T-cell hybrid require the immediate-early gene nur77.
Engagement of the T-cell antigen receptor (TCR) on immature thymic T cells induces death by apoptosis. Although several lines of evidence indicate that apoptosis requires de novo gene expression, little is known about the molecular pathways that mediate this response. Here we show that nur77 (refs 4-7), a zinc-finger transcription factor, is expressed in response to TCR engagement in immature T cells and T-cell hybrids. Antisense inhibition of nur77 expression prevents apoptosis in TCR-stimulated cells. nur77 is also expressed in response to mitogens, but in this case transcription is regulated by 5' upstream elements that are distinct from those used for induction of apoptosis. In addition, polyadenylation is only observed on nur77 transcripts found in condemned cells. These data support a role for nur77 in cell death that may be distinct from that of activation.
Liu
Z G
ZG
Department of Veterinary and Animal Sciences, University of Massachusetts, Amherst 01003.
Smith
S W
SW
McLaughlin
K A
KA
Schwartz
L M
LM
Osborne
B A
BA
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D001483:Base Sequence; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D006822:Hybrid Cells; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1; D012333:RNA, Messenger / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D018160:Receptors, Cytoplasmic and Nuclear; D011987:Receptors, Steroid; D012045:Regulatory Sequences, Nucleic Acid; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000378:metabolism*; D013950:Thymus Gland / Q000166:cytology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D014162:Transfection
D017931:DNA Primers; D004268:DNA-Binding Proteins; C539818:Nr4a1 protein, mouse; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1; D012333:RNA, Messenger; D011948:Receptors, Antigen, T-Cell; D018160:Receptors, Cytoplasmic and Nuclear; D011987:Receptors, Steroid; D014157:Transcription Factors