Figure 2.

Connexin-mediated negative control of cell proliferation. Cx43 negatively regulates cell growth by acting differently on activators (red) and inhibitors (blue) of cell proliferation. This regulation is mediated through various mechanisms in which Cx43 acts by itself (1), as a sequestrator (2) of growth regulators (e.g., CCN3, PTEN, Csk, c-Src), as a mediator of GJIC (3), through hemichannel activity (4) or its 20 kDa carboxyl tail (CT)-domain (5). These various mechanisms act on the nucleus (thick black arrows) to decrease cell proliferation. Some of these mechanisms are mediated by hemichannel or gap-junction permeability (thick blue arrows). Positive (+)/negative (−) effects of Cx43 on cell cycle regulators (p27, Cyclin D1, etc.) and c-Src effect on Cx43 are also shown (thin blue arrows).