EGF-Induced Gap Junction Degradation

Abstract

Gap junctions allow cytoplasmic molecules to move from one cell to another, and such communication appears to influence a broad range of processes, including development, cell proliferation, and behavior of cancer cells. Epidermal growth factor (EGF) is known to regulate conductance of gap junctions through mitogen-activated protein kinase-dependent phosphorylation of the connexin proteins that form gap junction channels. Leithe and Rivedal now present evidence that such phosphorylation may also promote internalization and proteasome-dependent degradation of connexin43 (Cx43). In a rat liver cell line, exposure of cells to EGF caused internalization and degradation of Cx43. Ubiquitination of Cx43 was also stimulated by EGF, and studies with proteasomal inhibitors implicated the proteasome in degradation of Cx43. Because loss of gap junction communication has been associated with carcinogenesis and enhanced EGF signaling also contributes to some forms of cancers, the authors note that the newly described regulatory pathway could have a role in tumorigenesis. E. Leithe, E. Rivedal, Epidermal growth factor regulates ubiquitination, internalization and proteasome-dependent degradation of connexin43. J. Cell Sci. 117 , 1211-1220 (2004). [Abstract] [Full Text]