Work

Proteasome inhibition attenuates rasfonin-induced autophagy concurring with the upregulation of caspase-dependent apoptosis

Year: 2016

Type: article

Abstract: Two major protein quality control mechanisms exist in eukaryotic cells, the ubiquitin-proteasome system (UPS) and the autophagy-lysosome system. Generally, the inhibition of UPS is believed to enhance autophagic pathway; nevertheless, the crosstalk between these two degradation systems may be much more complicated. Rasfonin, a 2-pyrone derivative of fungal secondary metabolites, is demonstrated to have the antitumor effect and can function as an autophagy inducer. Here, we reported that rasfonin activated multiple cell death pathways, including caspase-dependent apoptosis. Using electroscopy and microscopy, we observed rasfonin increased the formation of autophagosome. In immunoblotting assay, rasfonin enhanced autophagic flux concomitant with the upregulation of ubiquitination. MG132, an inhibitor of proteasome, attenuated rasfonin-dependent autophagy, whereas its presentation stimulated rasfonin-induced cleavage of poly (ADP-ribose) polymerase, a marker of caspase-dependent apoptosis. Together, we demonstrated that rasfonin induced the activation of both UPS and autophagic pathway, and the inhibition of UPS attenuated rasfonin-induced autophagy and enhanced the cytotoxicity of rasonin by upregulation of caspase-dependent apoptosis.

Source: Mycology&#58 An International Journal on Fungal Biology

DOI: 10.1080/21501203.2016.1147091

Authors: Siyuan Yan, Yongsheng Che, Xuejun Jiang

Institutions: Chinese Academy of Sciences, Institute of Microbiology, University of Chinese Academy of Sciences, State Key Laboratory of Mycology

Language: English

Topic: Autophagy in Disease and Therapy

Subfield: Epidemiology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $1,165