脂多糖诱导的肿瘤坏死因子(LITAF)生物学功能研究进展

Progress Advance on Biological Functions of LPS-induced TNF-α

脂多糖诱导的肿瘤坏死因子（LPS-induced TNF-α,LITAF）,又称p53诱导基因7或溶酶体/晚期内体小膜内在蛋白。早期研究认为,p53蛋白的164~170位氨基酸肽段导入到人体单核细胞后可抑制LITAF的表达。近期研究发现,LITAF在LPS诱导的单核细胞或巨噬细胞中作为炎症细胞因子TNF-α的转录激活剂起作用,进而引发炎症。典型的LITAF结构域包含N-端的CXXC区、25个氨基酸长的疏水区和C-端的（H）XCXXC区。当机体受到LPS刺激后,LITAF疏水区结合到胞膜上,将N-端和C-端的CXXC区域连接在一起,形成紧密结合的Zn2＋结构,此结构域诱导LITAF蛋白和STAT6（B）蛋白形成复合体进入细胞核,与TNF-α的启动子结合进而激活细胞因子TNF-α的转录表达,内源性增强机体清除肿瘤细胞或入侵病原的能力。该文就LITAF的结构和生物学功能的研究进展进行概述。

LPS-induced TNF-α（LITAF）, also known as p53-inducible gene 7（PIG7） or small integral membrane protein of the lysosome/late endosome（SIMPLE）, was initially demonstrated to be negatively regulated by p53 through specific binding to a heptamer（from 164 aa to 170 aa） in an LPS-stimulated human monocytes. Subsequent studies conformed that LITAF served as a transcriptional activator of inflammatory cytokine TNF-α towards LPS exposed monocytes or macrophages. The typical LITAF contains the N-terminal CXXC motif, followed by the hydrophobic region of 25 amino acids residues and the C-terminal（H）XCXXC knuckle. Two CXXC motifs will bind together and form a compact Zn2＋-binding structure in response to LPS exposure. The LITAF then enters into nucleus through recruiting STAT6（B） and subsequently induces TNF-α transcription by binding its promotor region. In this review, recent progress on LITAF structure and its biological function were summarized.