Cell polarity refers to the asymmetric distribution of cellular components between two distinct ends of metazoan cells. Loss of cell polarity represents one of the key hallmarks in cancer development. Scribble, a core polarity regulator can exert tumour suppressor or oncogenic properties during carcinogenesis. Deregulation of Scribble is also associated with poor prognosis in prostate and breast cancer. Scribble comprise of 16 Leucine Rich Repeats (LRR) and 4 PSD-95/Discs-large/ZO-1 (PDZ) domains, where the PDZ domains coordinate the majority of Scribble biological interactions. Hence the interplay between PDZ domains and Scribble ligands is key in determining Scribble function as an adaptor protein in orchestrating cellular signalling complexes. Nonetheless, the exact mechanistic regulatory system that governs PDZ domains interactions remains elusive.
Herein, we study Scribble interaction with a well-established binding partner βPIX; where their interaction regulates apoptosis and exocytosis pathways. We characterised the mechanism of Scribble PDZ domains interaction with βPIX using biochemical assays and structural methods.