Ghosh, Debasish Kumar (2018) The ATPase VCP/p97 functions as a disaggregase against toxic Huntingtin-exon1 aggregates. FEBS Letters, 592 (16). pp. 2680-2692. ISSN 0014-5793

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Abstract

Intracellular protein aggregation is characterized by accumulation of misfolded proteins. Chaperones, degradation machineries, and quality-control mechanisms counteract protein aggregation. In this study, we report that the ATPase valosin-containing protein (VCP/p97) acts as a functional disaggregase that disassembles Huntingtin-exon1 aggregates in vitro and in HeLa cells. The N-terminal part of VCP (Cdc48_N domain) interacts with the N-terminal 17-amino acid region of Huntingtin-exon1. We show that VCP has properties of a disaggregase, since it is capable of reducing preformed protein aggregates and displays increased ATPase activity in the presence of protein aggregates. However, VCP shows high divergence/disparity from other disaggregases. Taken together, our studies show the novel function of VCP/p97 as a disaggregase which detangles protein aggregates to probably channelize their degradation.

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