The role of connexins in controlling cell growth and gene expression.

The purpose of this paper is to provide a brief overview of current thinking on the role of connexins, in particular Cx43, in growth regulation, and a more detailed discussion as to potential mechanisms involved with an emphasis on gene expression. While the precise molecular mechanism by which connexins can affect the growth of normal or tumor cells remains elusive, a number of exciting reports have expanded our understanding and are presented in some detail. Thus, we will discuss (Section 2): the role of protein-protein interactions in integrating connexins into multiple signal transduction pathways; phosphorylation at specific sites and reversal of growth inhibition; the role of the carboxy-terminal regulatory domain as a signaling molecule. Some of our latest work on the potential functions of endogenously produced carboxy-terminal fragments of Cx43 are also presented (Section 3). Finally, Section 4 will pay tribute to the rapidly emerging realization that connexins such as Cx43 and Cx32 exert important and extensive effects on gene expression, particularly those genes linked to growth regulation.