Rothenberger S, Rousseaux M, Knecht H, Bender F C, Legler D F, Bron C
Institute of Biochemistry, University of Lausanne, Epalinges, Switzerland.
Cell Mol Life Sci. 2002 Jan;59(1):171-80. doi: 10.1007/s00018-002-8413-y.
The latent membrane protein 1 (LMP1) encoded by the Epstein-Barr virus acts like a constitutively activated receptor of the tumor necrosis factor receptor (TNFR) family and is enriched in lipid rafts. We showed that LMP1 is targeted to lipid rafts in transfected HEK 293 cells, and that the endogenous TNFR-associated factor 3 binds LMP1 and is recruited to lipid rafts upon LMP1 expression. An LMP1 mutant lacking the C-terminal 55 amino acids (Cdelta55) behaves like the wild-type (WT) LMP1 with respect to membrane localization. In contrast, a mutant with a deletion of the 25 N-terminal residues (Ndelta25) does not concentrate in lipid rafts but still binds TRAF3, demonstrating that cell localization of LMP1 was not crucial for TRAF3 localization. Moreover, Ndelta25 inhibited WT LMP1-mediated induction of the transcription factors NF-kappaB and AP-1. Morphological data indicate that Ndelta25 hampers WT LMP1 plasma membrane localization, thus blocking LMP1 function.
爱泼斯坦-巴尔病毒编码的潜伏膜蛋白1(LMP1)的作用类似于肿瘤坏死因子受体(TNFR)家族的组成型激活受体,并在脂筏中富集。我们发现,LMP1在转染的人胚肾293细胞中定位于脂筏,并且内源性TNFR相关因子3与LMP1结合,并在LMP1表达时被募集到脂筏中。一个缺失C末端55个氨基酸(Cdelta55)的LMP1突变体在膜定位方面的表现与野生型(WT)LMP1相似。相比之下,一个缺失25个N末端残基(Ndelta25)的突变体并不集中在脂筏中,但仍能结合TRAF3,这表明LMP1的细胞定位对TRAF3的定位并不关键。此外,Ndelta25抑制了WT LMP1介导的转录因子NF-κB和AP-1的诱导。形态学数据表明,Ndelta25阻碍了WT LMP1在质膜上的定位,从而阻断了LMP1的功能。