FUNCTIONAL MYC-MAX HETERODIMER IS REQUIRED FOR ACTIVATION-INDUCED APOPTOSIS IN T-CELL HYBRIDOMAS

T cell hybridomas respond to activation signals by undergoing apoptoti c cell death, and this is likely to represent comparable events relate d to tolerance induction in immature and mature T cells in vivo. Previ ous studies using antisense oligonucleotides implicated the c-Myc prot ein in the phenomenon of activation-induced apoptosis. This role for c -Myc in apoptosis is now cofirmed in studies using a dominant negative form of its heterodimeric binding partner, Max, which we show here in hibits activation-induced apoptosis. Further, coexpression of a recipr ocally mutant Myc protein capable of forming functional heterodimers w ith the mutant Max can compensate for the dominant negative activity a nd restore activation-induced apoptosis. These results imply that Myc promotes activation-induced apoptosis by obligatory heterodimerization with Max, and therefore, by regulating gene transcription.