Browsing by Author "Sjöblad, Tiia"

Degradation of cellular proteins in the ubiquitin-proteasome system regulates various biological processes. It has also been implicated in the pathogenesis of numerous diseases, such as cancer and neurodegenerative diseases. Ubiquitin-specific proteases (USP) are involved in the deubiquitination of protein. The small-molecule inhibitor IU1, specific for USP14 has previously been shown to activate AMPK in HC cells. In this study we further explore the connection between IU1 and AMPK. Huh7 and HEK293 cells were treated with IU1 for variable time periods. Western blotting was applied to investigate the protein phosphorylation level (i.e. activation) of AMPK. We found that IU1 activates AMPK in Huh7 cells, but has no apparent effect in HEK293 cells. By assessing the mitochondria respiration we found evidence proposing IU1 inhibits complex I. Our results suggests that IU1 activates AMPK in certain cell lines with the possible underlying mechanism being the inhibition of complex I of the respiratory chain.