Garscube Estate

The autophagy-lysosome pathway maintains cellular homeostasis and protects against neurodegenerative disorders. Recent findings show that autophagy can be impaired in these diseases, and that the cell activates an alternative Golgi-mediated degradation pathway, leading to expulsion of toxic protein aggregates. Ultimately this process leads to nuclear breakdown and neuronal cell death.

Recent next-generation-sequencing studies demonstrate that multiple pathways are often deregulated in advanced and metastatic prostate cancer (PC). In a recent issue of The Journal of Pathology, an elegant study by Jefferies et al used in vivo modelling to demonstrate how activation of the PI3K, WNT and MAPK pathway converges on mTORC1 signalling to drive aggressive disease.

Identification of Selective UbVs for RING and U-box E3s   Inhibition by UbV.pCBL Relies on Tyr371-Phosphorylation of CBL UbV.XR binds selectively to the RING domain of XIAP (residues 434–C, referred to as XR), but not the RING domain of BIRC2 (residues 555–C, referred to as B2R), and stimulates autoubiquitination of XR (Figure 1Figure 1). To validate these findings, we performed single-turnover lysine discharge assays using UbV.XR with XR or B2R.