Spautin-1 is a specific and potent autophagy inhibitor (IC50=0.74µM). It promotes the degradation of Vps34 PI3 kinase complexes by inhibiting two ubiquitin specific peptidases, USP10 and USP13, that target the Beclin1 subunit of Vps34 complexes. Since USP10 mediates the deubiquitination of p53, regulating deubiquitination activity of USP10 and USP13 by Beclin1 provides a mechanism for Beclin1 to control the levels of p53. By this mechanism, Spautin-1 increased cancer cell death in the setting of nutrient deprivation when autophagy would normally act as a survival mechanism in these metabolically stressed cells.

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