Bissonnette R P, McGahon A, Mahboubi A, Green D R
La Jolla Institute for Allergy and Immunology, California 92037.
J Exp Med. 1994 Dec 1;180(6):2413-8. doi: 10.1084/jem.180.6.2413.
T cell hybridomas respond to activation signals by undergoing apoptotic cell death, and this is likely to represent comparable events related to tolerance induction in immature and mature T cells in vivo. Previous studies using antisense oligonucleotides implicated the c-Myc protein in the phenomenon of activation-induced apoptosis. This role for c-Myc in apoptosis is now confirmed in studies using a dominant negative form of its heterodimeric binding partner, Max, which we show here inhibits activation-induced apoptosis. Further, coexpression of a reciprocally mutant Myc protein capable of forming functional heterodimers with the mutant Max can compensate for the dominant negative activity and restore activation-induced apoptosis. These results imply that Myc promotes activation-induced apoptosis by obligatory heterodimerization with Max, and therefore, by regulating gene transcription.
T细胞杂交瘤通过经历凋亡性细胞死亡对激活信号作出反应，这可能代表了体内未成熟和成熟T细胞中与耐受性诱导相关的类似事件。先前使用反义寡核苷酸的研究表明c-Myc蛋白与激活诱导的凋亡现象有关。现在，在使用其异二聚体结合伴侣Max的显性负性形式的研究中证实了c-Myc在凋亡中的这一作用，我们在此表明该形式可抑制激活诱导的凋亡。此外，能够与突变型Max形成功能性异二聚体的相互突变的Myc蛋白的共表达可以补偿显性负性活性并恢复激活诱导的凋亡。这些结果表明，Myc通过与Max形成必需的异二聚体，进而通过调节基因转录来促进激活诱导的凋亡。
