Requirement for the orphan steroid receptor Nur77 in apoptosis of T-cell hybridomas.
Apoptosis is a phenomenon observed during development of many cell types in many organisms. It is an internal, programmed cell death characterized by DNA fragmentation into nucleosome-size pieces. Anti-CD3-induced apoptosis in T-cell hybridomas and immature thymocytes requires new gene transcription and may be related to negative selection during T-cell development. Using subtractive hybridization, we isolated a complementary DNA clone encoding the orphan steroid receptor Nur77 (refs 7-9). It shows different patterns of messenger RNA induction between apoptotic and stimulated T cells. We report here the use of gel shift analysis to demonstrate that the Nur77 protein is present at high levels in apoptotic T-cell hybridomas and apoptotic thymocytes, but not in growing T cells or stimulated splenocytes. A Nur77 dominant negative protected T-cell hybridomas from activation-induced apoptosis. Hence Nur77 is necessary for induced apoptosis in T-cell hybridomas.
Woronicz
J D
JD
Department of Molecular and Cell Biology, University of California, Berkeley 94720.
Calnan
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D017209:Apoptosis / Q000235:genetics / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D006825:Hybridomas / Q000378:metabolism / Q000502:physiology*; D009154:Mutation; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1; D018160:Receptors, Cytoplasmic and Nuclear; D011987:Receptors, Steroid / Q000235:genetics / Q000502:physiology*; D013601:T-Lymphocytes / Q000378:metabolism / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*
D004268:DNA-Binding Proteins; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1; D018160:Receptors, Cytoplasmic and Nuclear; D011987:Receptors, Steroid; D014157:Transcription Factors