Towards a structural understanding of the cell polarity regulator and tumour suppressor protein, Scribble (#375)
Cell polarity or cell asymmetry is crucial for the normal biological function of all metazoan cells. Loss of cell polarity disrupts cellular organisation that represents one of the key hallmarks of cancer progression. A core polarity module named SCRIB is found to be involved in the establishment and maintenance of cell polarity. Scribble, a member of the SCRIB module is deregulated in many cancers such as breast, cervical and prostate cancer. Scribble belongs to the Leucine Rich Repeat and PDZ domain (LAP) family that consists of 16 Leucine Rich Repeats (LRR) at the N-terminus and 4 PSD-95/Discs-large/ZO-1 (PDZ) domains at the C-terminus. These domains allow Scribble to associate with different molecules to orchestrate various signalling pathways.
This study investigates Scribble’s mechanism of action using a key binding partner, βPIX. βPIX is a PAK-interacting exchange factor beta that has been shown to interact with Scribble during exocytosis, neuronal transmission and directed cell migration. In this study we expressed, purified and characterised each individual Scribble domains and evaluated their interactions with βPIX using multiple biochemical methods.