Recessive mutations in a common pathway block thymocyte apoptosis induced by multiple signals

Francis A. Flomerfelt, Roger L. Miesfeld

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Abstract

The glucocorticoid receptor (GR) is a ligand-regulated transcription factor that controls genes necessary to initiate glucocorticoid-induced thymocyte apoptosis. We have performed a genetic analysis of thymocyte cell death by isolating and characterizing a panel of GR+ dexamethasone-resistant mutants of the murine WEHI7.2 thymocyte cell line. These apoptosis-defective (Apt-) mutants were used to identify previously unknown early steps in the apoptotic pathway. The Apt- mutants contain nonglucocorticoid receptor, recessive mutations in genes that represent multiple complementation groups. These mutations block apoptosis induced by dexamethasone, gamma irradiation, and c-AMP treatment before the point where Bcl-2 exerts its protective effect. We propose that different signals share a common apoptotic pathway, and that the induction of apoptosis involves multiple precommitment steps that can be blocked by recessive mutations.

Original languageEnglish (US)
Pages (from-to)1729-1742
Number of pages14
JournalJournal of Cell Biology
Volume127
Issue number6 I
DOIs
StatePublished - Dec 1 1994

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ASJC Scopus subject areas

  • Cell Biology

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