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

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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.