Connexin43 interacts with NOV: a possible mechanism for negative regulation of cell growth in choriocarcinoma cells.
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Gellhaus A, Dong X, Propson S, Maass K, Klein-Hitpass L, Kibschull M, Traub O, Willecke K, Perbal B, Lye SJ, Winterhager E
Connexin43 interacts with NOV: a possible mechanism for negative regulation of cell growth in choriocarcinoma cells.
J Biol Chem. 2004 Aug 27;279(35):36931-42. Epub 2004 Jun 4.
- PubMed ID
- 15181016 [ View in PubMed]
- Abstract
The gap junction protein connexin43 (Cx43) is thought to be involved in growth control in several tissues. Using the doxycycline inducible tet-on system, we generated human malignant trophoblast Jeg3 cells transfected with either Cx40, Cx43, or C-terminal truncated Cx43 (trCx43). Cx43, but not Cx40 or trCx43, displayed a reduced cell growth of Jeg3 cells in vitro and tumor growth in nude mice, suggesting a role of the C terminus of Cx43 in growth regulation. Using gene array analysis, the growth regulator NOV (CCN3), a member of the CCN gene family, was found to be up-regulated only in the Cx43-transfected cells. Validation by reverse transcriptase-PCR confirmed an up-regulation of the NOV transcript exclusively upon Cx43 induction. In contrast to Cx40 or trCx43, induction of Cx43 led to a switch in localization of NOV from the nucleus to the cell membrane, where it is colocalized with Cx43. Coimmunoprecipitation showed a binding of NOV to the C terminus of Cx43 in vitro as well as in transfected cells. Jeg3 cells transfected only with NOV revealed that NOV itself acts as a growth regulator. We suggest that Cx43 is able to regulate cell growth via an up-regulation of NOV transcription, a change in localization of the NOV protein and a binding of NOV to the C terminus of Cx43.