Huntingtin-interacting protein 1 protein interactor (HIPPI) shows a specific function of binding to free hunfingtin-interacting protein 1 (HIP-1) to form pro-apeptotic 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 caspases and the release of cytochrome C and apoptosis-inducing factor (AIF) from mitochondria.In addition,HIPPI interacts with a specific 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.
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