细胞凋亡途径中HIPPI的潜在调节作用

Potential regulation of HIPPI in cell apoptosis

亨廷顿蛋白相互作用蛋白1相互作用因子（huntingtin-interacting protein 1 protein interactor，HIPPI）也称为雌激素相关受体β样蛋白1（estrogen-related receptor beta-like protein 1，ESRRBLl）或者鞭毛内转运蛋白57同系物（intraflagellar transport 57 homolog，IFT57）。2002年，Gervais等在研究亨廷顿病（Huntington disease，HD）的发病机制时，发现了一种新的与享廷顿蛋白相互作用蛋白1（hunting-tin-interacting protein 1，HIP-1）相互作用的蛋白，进而克隆了该蛋白的基因，并命名这个新的蛋白为HIPPI。

Huntingtin-interacting protein 1 protein interactor （HIPPI） shows a specific function of binding to free huntingtin-interacting protein 1 （ HIP-1 ） to form pro-apoptotic HIPPI-HIP1 heterodimers. This heterodimer recruits procaspase-8 into a complex of HIPPI, HIP1 and procaspase-8, and launches apoptosis-through components of the extrinsic cell-death pathway. Exogenous expression of HIPPI in culture cell lines leads to the activation of several easpases and the release of cytochrome C and apoptosis-indueing factor （AIF） from mitochondria. In addition, HIPPI interacts with a speci- fic 9-bp sequence motif, which is defined as the HIPPI binding site （HBS）, presents in the upstream promoters of caspase- 1 and other genes, and regulates their expression. The extensive distribution of HIPPI in human tissues and the excessive content in the neurons of human brain suggest that HIPPI possesses important biological function and has associated with the mechanisms of neurodegeneration in Huntington＇s disease. In the present review, we focus on the properties of HIPPI gene and HIPPI, the distribution and expression in human tissues, the biological functions and the pathological mechanism of the molecule.