肿瘤坏死因子受体相关因子2（TRAF2）对c-Jun氨基末端激酶（JNK）的激活至关重要，但对核因子κB（NF-κB）的激活并非如此，并且它调节淋巴细胞的增殖和存活。

TRAF2 is essential for JNK but not NF-kappaB activation and regulates lymphocyte proliferation and survival.

作者信息

Lee S Y, Reichlin A, Santana A, Sokol K A, Nussenzweig M C, Choi Y

机构信息

Laboratory of Immunology, The Rockefeller University, New York, New York 10021, USA.

出版信息

Immunity. 1997 Nov;7(5):703-13. doi: 10.1016/s1074-7613(00)80390-8.

DOI:10.1016/s1074-7613(00)80390-8

PMID:9390693

Abstract

TRAF2 is believed to mediate the activation of NF-kappaB and JNK induced by the tumor necrosis factor receptor (TNFR) superfamily, which elicits pleiotropic responses in lymphocytes. We have investigated the physiological roles of TRAF2 in these processes by expressing a lymphocyte-specific dominant negative form of TRAF2, thereby blocking this protein's effector function. We find that the TNFR superfamily signals require TRAF2 for activation of JNK but not NF-kappaB. In addition, we show that TRAF2 induces NF-kappaB-independent antiapoptotic pathways during TNF-induced apoptosis. Inhibition of TRAF2 leads to splenomegaly, lymphadenopathy, and an increased number of B cells. These findings indicate that TRAF2 is involved in the regulation of lymphocyte function and growth in vivo.

摘要

据信，肿瘤坏死因子受体（TNFR）超家族诱导的核因子κB（NF-κB）和c-Jun氨基末端激酶（JNK）的激活由肿瘤坏死因子受体相关因子2（TRAF2）介导，这在淋巴细胞中引发多效性反应。我们通过表达淋巴细胞特异性的显性负性形式的TRAF2，从而阻断该蛋白的效应器功能，研究了TRAF2在这些过程中的生理作用。我们发现，TNFR超家族信号在激活JNK时需要TRAF2，但激活NF-κB时则不需要。此外，我们表明，在肿瘤坏死因子（TNF）诱导的细胞凋亡过程中，TRAF2诱导不依赖NF-κB的抗凋亡途径。抑制TRAF2会导致脾肿大、淋巴结病以及B细胞数量增加。这些发现表明，TRAF2参与体内淋巴细胞功能和生长的调节。