Research Grant Award

Chih-Cheng Tsai, PhD

UMDNJ-Robert Wood Johnson Medical School
Boat, an AXH domain protein, suppresses the cytotoxicity of Ataxin-1

In this proposal, we provide evidence showing that the cytotoxicity caused by mutant ataxin-1 is ameliorated by its association with an ataxin-1 related protein, which we have named Brother of ataxin-1 (Boat). We first identified Boat through the discovery that it shares a conserved protein domain with ataxin-1. Through characterization of Boat, we discovered that Boat interacts with ataxin-1 and that their interaction perturbs the ability of ataxin-1 to self aggregate. We investigated the physiological relevance of the interaction between Boat and ataxin-1 in fruit fly (Drosophila) and discovered that the propensity of mutant ataxin-1 to form protein aggregates in Drosophila salivary glands and to cause deformity in Drosophila eye are both suppressed by Boat. Our finding that Boat can suppress the cytotoxicity of ataxin-1 unravels another layer of the mechanism involved in modulating the pathological effects of mutant ataxin-1 and paves ways for designing therapeutic strategies to treat SCA 1.