Cancer Cell Biology
Area of interest
Rubenstein Lab: Regulation of Keratinocyte Adherens Junctions and Desmosomes.
b-catenin and plakoglobin are constituents of the adherens junction cell-cell adhesion complex. Plakoglobin also forms part of the desmosome cell-cell adhesion complex. In addition to functioning in cell-cell adhesion, b-catenin and plakoglobin act downstream of frizzled cell surface receptors to mediate Wnt signaling. Human disease results from aberrant regulation of the adhesion and signaling functions of these proteins. For example, (1) b-catenin's signaling function is constitutively activated in human cancers including colorectal carcinoma and melanoma and (2) desmogleins, constituents of the desmosome to which plakoglobin binds, are the target antigens for autoantibodies produced in the autoimmune blistering diseases pemphigus vulgaris and pemphigus foliaceus.
My lab is interested in understanding (1) how cells regulate their ability to adhere to one another, (2) how cell-cell adhesion complexes might also function to transduce signals that inform the cell about the state of adhesion, a process known as signal transduction, and (3) the relationship of these regulatory events to human neoplastic and autoimmune skin disease. Current projects in the lab focus on the human proteins b-catenin and plakoglobin, and the related fruit fly protein Armadillo. We are studying the cell-cell adhesion and signaling functions of adherens junctions and desmosomes and how these processes are regulated by phosphorylation and O-glycosylation