The FAM deubiquitylating enzyme localizes to multiple points of protein trafficking in epithelia, where it associates with E-cadherin and β-catenin

Ubiquitylation is a necessary step in the endocytosis and lysosomal trafficking of many plasma membrane proteins and can also influence protein trafficking in the biosynthetic pathway. Although a molecular understanding of ubiquitylation in these processes is beginning to emerge, very little is known about the role deubiquitylation may play. Fat Facets in mouse (FAM) is substrate-specific deubiquitylating enzyme highly expressed in epithelia where it interacts with its substrate, β-catenin. Here we show, in the polarized intestinal epithelial cell line T84, FAM localized to multiple points of protein trafficking. FAM interacted with β-catenin and E-cadherin in T84 cells but only in subconfluent cultures. FAM extensively colocalized with β-catenin in cytoplasmic puncta but not at sites of cell-cell contact as well as immunoprecipitating with β-catenin and E-cadherin from a higher molecular weight complex (~500 kDa). At confluence FAM neither colocalized with, nor immunoprecipitated, β-catenin or E-cadherin, which were predominantly in a larger molecular weight complex (~2 MDa) at the cell surface. Overexpression of FAM in MCF-7 epithelial cells resulted in increased β-catenin levels, which localized to the plasma membrane. Expression of E-cadherin in L-cell fibroblasts resulted in the relocalization of FAM from the Golgi to cytoplasmic puncta. These data strongly suggest that FAM associates with E-cadherin and β-catenin during trafficking to the plasma membrane.

Ruling Class Men: Money, Sex, Power

What is it like to be a master of the universe? The authors have researched the desires and fears of the world's most powerful men. The Murdochs, Packers, Kennedys, Agnellis and other men like them, directly determine the fates of thousands and influence the future of the world like no other people. Described as 'sacred monsters' by one of their own, they are carefully created to be what they are and to enjoy shaping the world in their own likeness. To learn about these often reclusive men, the authors extended the life-history technique to interrogate autobiographies, diaries and biographies and have created a composite picture, a collective portrait, of tycoons over three generations. The book carefully explores the childhoods, schooling, work and play, sexual activities, marriages and deaths of the wealthiest men who have ever lived. It exposes the nature of ruling-class masculinity itself.