HIP1 and the Promotion of Neoplasia

亨廷顿蛋白相互作用蛋白1(Huntingtin Interaction Protein 1，HIP1)是一种可能参与细胞周期蛋白和肌醇结合的脂质结合蛋白。 由于亨廷顿蛋白与亨廷顿蛋白的相互作用，这种蛋白质在亨廷顿病中发生了突变。它是 发现致癌的HIP1/PDGF_R融合蛋白也与白血病有关，该融合蛋白是由一种 慢性粒单核细胞白血病(CMML)患者T(5；7)染色体易位。 我们假设HIP1参与肿瘤的发生还有另外三个原因。第一，HIP1部分 HIP1/PDGFI3R融合蛋白是细胞转化所必需的。其次，HIP1在 多发性肿瘤(初步数据部分)。HIP1显性负性突变体的表达 (初步数据部分)或HIP1基因缺失会导致细胞凋亡。 我们提出的第一个假设是HIP1是致癌的，它在体内的过度表达导致 癌症。作为推论，我们预测，当HIP1不表达时，将减少对 癌症的发展。其次，我们建议检验髋关节LR补充髋关节1功能的假设(S) 在内吞、细胞生长和癌变中起重要作用。最后，我们建议检验这样一个假设，即监管 网状蛋白介导的HIP1和HIPlr的转运导致生长因子受体(GFR)信号的增加。 我们认为这可能是通过增加细胞表面受体的数量来实现的。 对生长因子的敏感性，从而促进细胞存活和/或生长。

Huntingtin Interacting Protein 1 (HIP1) is a clathrin and inositol lipid binding protein that may be involved in neurodegeneration by virtue of its interaction with huntingtin, the protein mutated in Huntington's disease. It is also associated with leukemia by discovery of the oncogenic HIP1/PDGF_R fusion protein that resulted from a t(5;7) chromosomal translocation in a patient with chronic myelomonocytic leukemia (CMML). We hypothesize that HIP1 is involved in tumorigenesis for three additional reasons. First, the HIP1 portion of the HIP1/PDGFI3R fusion protein is necessary for cellular transformation. Second, HIP1 is over-expressed in multiple tumors (preliminary data section). Third, expression of a dominant negative mutant of HIP1 (preliminary data section) or genetic deletion of HIP1 leads to apoptosis. The first hypothesis we propose to test is that HIP 1 is tumorigenic and its over-expression in vivo leads to cancer. As a corollary, we predict that when HIP1 is not expressed, there will be a diminished susceptibility to the development of cancer. Second, we propose to test the hypothesis that HIP lr complements HIP 1 function(s) in endocytosis, cell growth and carcinogenesis. Finally, we propose to test the hypothesis that regulation of clathrin mediated trafficking by HIP1 and HIPlr results in an increase in growth factor receptor (GFR) signaling. We suggest that this maybe accomplished by increasing the number of the cell surface receptors to increase sensitivity to growth factor and thereby promote cellular survival and/or growth.