8.A.160.  The Catenin (Catenin) Family 

Catenin δ-1 is a key regulator of cell-cell adhesion that associates with and regulates the cell adhesion properties of C-, E- and N-cadherins, being critical for their surface stability (Davis et al. 2003, Ishiyama et al. 2010). Beside cell-cell adhesion, it regulates gene transcription through several transcription factors including ZBTB33/Kaiso2 and GLIS2, and the activity of Rho family GTPases and downstream cytoskeletal dynamics (Daniel and Reynolds 1999, Ishiyama et al. 2010). It is implicated in both cell transformation by SRC and ligand-induced receptor signaling through the EGF, PDGF, CSF-1 and ERBB2 receptors (Hosking et al. 2007). Mutations in the beta-catenin gene (CTNNB1), lead to aberrant immunohistochemical expression of beta-catenin, and this represents a key mechanism of WNT/beta-catenin pathway alteration in ovarian cancer (Angelico et al. 2021). Beta-catenin and AQP1 are co-expressed in a sub-group of ovarian tumors and play important roles in carcinogenesis (Angelico et al. 2021).

p120 catenin recruits human papillomavirus (HPV) to the transmembrane protease, gamma-secretase, to promote virus infection (Harwood et al. 2020). During internalization and trafficking, HPV moves from the cell surface to the endosome where γ-secretase promotes insertion of the viral L2 capsid protein into the endosomal membrane. Protrusion of L2 through the endosomal membrane into the cytosol allows the recruitment of cytosolic host factors that target the virus to the Golgi, en route for productive infection. Cytosolic p120 catenin, likely via an unidentified transmembrane protein, interacts with HPV at early time-points during viral internalization and trafficking. In the endosome, p120 is not required for low pH-dependent disassembly of the HPV L1 capsid protein from the incoming virion. Rather, p120 is required for HPV to interact with gamma-secretase - an interaction that ensures the virus is transported along a productive route (Harwood et al. 2020).