Lee Z H, Lee S E, Kwack K, Yeo W, Lee T H, Bae S S, Suh P G, Kim H H
National Research Laboratory for Bone Metabolism and Research Center for Proteineous Materials, Chosun University School of Dentistry, Kwangju, Korea.
J Leukoc Biol. 2001 Mar;69(3):490-6.
The tumor necrosis factor receptor (TNFR)-associated factor (TRAF) proteins play a central role in the early steps of signal transduction by TNFR superfamily proteins, which induce various cellular responses, including apoptosis. Influences of TRAF proteins on the regulation of cell death and physical interactions between TRAFs and caspases have been reported. In this study, we demonstrate that TRAF3 is proteolyzed during cell death in a caspase-dependent manner. TRAF3 was found to be cleaved by incubation with caspase3 in vitro and by Fas- or CD3-triggering in Jurkat-T cells. The Fas- or CD3-induced cleavage of TRAF3 was blocked by caspase inhibitors and by introduction of alanine substitutions for D347 and D367 residues. Furthermore, the amino-terminal fragment of TRAF3 showed a different intracellular localization from the full-length TRAF3 with preferential distribution to particulate fractions and the nucleus. These findings suggest that TRAF3 may be regulated by caspases during apoptosis of T cells.
肿瘤坏死因子受体（TNFR）相关因子（TRAF）蛋白在TNFR超家族蛋白信号转导的早期步骤中起核心作用，TNFR超家族蛋白可诱导包括凋亡在内的各种细胞反应。已有报道称TRAF蛋白对细胞死亡调节的影响以及TRAF与半胱天冬酶之间的物理相互作用。在本研究中，我们证明TRAF3在细胞死亡过程中以半胱天冬酶依赖性方式被蛋白酶解。发现TRAF3在体外与半胱天冬酶3孵育时以及在Jurkat - T细胞中被Fas或CD3触发时被切割。半胱天冬酶抑制剂以及将D347和D367残基替换为丙氨酸可阻断Fas或CD3诱导的TRAF3切割。此外，TRAF3的氨基末端片段与全长TRAF3的细胞内定位不同，优先分布于颗粒部分和细胞核。这些发现表明，在T细胞凋亡过程中，TRAF3可能受半胱天冬酶调节。
