Nov 2, 2018

Cantharidin alters GPI-anchored protein sorting by targeting Cdc1 mediated remodeling in Endoplasmic Reticulum

BioRxiv : the Preprint Server for Biology
Raghuvir Singh Tomar, Pushpendra Kumar Sahu

Abstract

Cantharidin (CTD) is a potent anticancer small molecule produced by several species of blister beetle. It has been a traditional medicine for the treatment of warts and tumors for many decades. CTD suppresses the tumor growth by inducing apoptosis, cell cycle arrest, and DNA damage. It is a known inhibitor of PP2A and PP1. In this study, we identified new molecular targets of CTD using Saccharomyces cerevisiae as a model organism which expresses a Cantharidin Resistance Gene (CRG1). CRG1 encodes a SAM-dependent methyltransferase that inactivates CTD by methylation. CTD alters lipid homeostasis, cell wall integrity, endocytosis, adhesion, and invasion in yeast cells. We found that CTD specifically affects the phosphatidylethanolamine (PE) associated functions which can be rescued by supplementation of ethanolamine (ETA) in the growth media. CTD also perturbed ER homeostasis and cell wall integrity by altering the GPI-anchored protein sorting. The CTD dependent genetic interaction profile of CRG1 revealed that Cdc1 activity in GPI-anchor remodeling is the key target of CTD, which we found to be independent of PP2A and PP1. Furthermore, our experiments with human cells suggest that CTD functions through a conserved mechanism in hi...Continue Reading

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Mentioned in this Paper

Study
CDC1 protein, S cerevisiae
Endocytosis
Pulmonary Embolism
Protein Methylation
PP1 Antibody
Protein Sorting
Saccharomyces cerevisiae allergenic extract
Lipid Homeostasis
THUMPD2 gene

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