Abstract C203: Cracking the (ultra)structural biology of Scribble to understand its role as a cell polarity regulator and tumor suppressor protein

Abstract

Cell polarity or cell asymmetry is crucial for the normal biological function of all metazoan cells. Loss of cell polarity disrupts cellular organization that represents one of the hallmarks of cancer progression. Scribble, a member of the core polarity SCRIB module is deregulated in many cancers such as breast cancer, cervical cancer and prostate cancer. Scribble is a member of the LAP family that consists of 16 Leucine Rich Repeats and 4 PSD-95/Discs-large/ZO-1 (PDZ) domains. The PDZ domains (4PDZ) in particular are important in Scribble's interactions with molecules that are involved in many crucial signaling pathways. We hypothesized that Scribble acts as a scaffold protein to orchestrate these interactions. Our aim is to decipher Scribble's mechanism of action through characterization of Scribble interactions with βPIX (PAK-interacting exchange factor beta), which is well establish in exocytosis and neuronal transmission. Herein, we used pull down assay, isothermal titration calorimetry and small angle X-ray scattering to unravel the interaction profile of the region of Scribble encoding for all four PDZ domains. Our study proposes a working model to illustrate how PDZ domains modulate Scribble and βPIX interactions. Citation Format: Krystle YB Lim, Sofia Caria, Colin M. House, Nathan J. Godde, Allison J. Ogden, Patrick O. Humbert, Marc Kvansakul. Cracking the (ultra)structural biology of Scribble to understand its role as a cell polarity regulator and tumor suppressor protein. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2015 Nov 5-9; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2015;14(12 Suppl 2):Abstract nr C203.