Analyses of HAP1/STB functions in regulation of cell-cycle progression and cellular stress responses

亨廷顿蛋白相关蛋白1（Huntingtin-associated protein 1，HAP 1）是细胞质包涵体（stigmoid body，STB）的核心分子。首先，我们研究了细胞周期依赖的变化，在HAP 1转染的HeLa细胞中的HAP 1分布。在分裂间期，HAP 1形成大尺寸的STBs。在有丝分裂过程中，大多数HAP 1/STB消失，但HAP 1的一个子集集中在纺锤体两极。当细胞进入胞质分裂时，HAP 1开始形成小尺寸的STB样包涵体。接下来，我们研究了应激暴露对HAP 1转染的永生化小鼠下丘脑细胞系中HAP 1/STB形态的影响。HAP 1在大多数应力条件下形成典型的STB（例如，热休克、ER应激和血清饥饿）。而在蛋白酶体抑制条件下，HAP 1诱导胞浆腺网状簇而不是STB的形成。目前，我们正在分析HAP 1/STB形态学改变的机制及其在蛋白酶体抑制剂诱导的细胞凋亡中的生物学意义。

Huntingtin-associated protein 1 is a core molecule of the cytoplasmic inclusion, stigmoid body (STB). First, we examined cell-cycle dependent change in HAP1 distribution in HAP1-transfected HeLa cells. In interphase, HAP1 formed large-sized STBs. During mitosis, most of the HAP1/STB disappeared but a subset of HAP1 was concentrated at the spindle poles. When cells entered cytokinesis, HAP1 started to form small-sized STB-like inclusion. Next, we examined effect of stress exposures on HAP1/STB morphology in HAP1-transfected immortalized mouse hypothalamic cell line. HAP1 formed typical STBs in most of the stress conditions (e.g., heat shock, ER stress and serum-starvation). However, in proteasome inhibited condition, HAP1 induced cytoplasmic glanulo-reticular clusters instead of STB formation. Now we are analyzing the mechanism of change in HAP1/STB morphology and its biological significance in proteasome-inhibitor-induced apoptosis.