Regulation of and regulation by CD44: a paradigm for complex regulatory networks

CD44 is expressed on the cell surface of lymphocytes and other hematopoietic and non-hematopoietic cells, where regulates cell-cell and environment-cell interactions by binding different components of extracellular matrix. CD44 is implicated in several other cellular processes, such as regulation of growth, survival, differentiation and motility, both under physiological and pathologic conditions. Studies on CD44-null or transgenic mice also established its involvement in diseases such as cancer, atherosclerosis and myocardial infarction. Its regulation involves several control mechanisms among which a fundamental role is played by alternative splicing of its pre-mRNA and by post-translational modifications. Here we review the mechanisms of regulation upstream and downstream of CD44