The polycomb group gene product Mel-18 interacts with cyclin D2 and modulates its activity.

Considerable evidence supports the view that D-type cyclins play a role in G1-S progression. We found that cyclin D2 directly interacts with Mel-18, one of the polycomb group gene products in a yeast two hybrid screen. Further, we have determined the binding domains that are required for interaction between cyclin D2 and Mel-18. The proline/serine-rich domain (P/S domain) of Mel-18 is required to interact with cyclin D2, and the N-terminal region of cyclin D2 is necessary to interact with Mel-18. A co-localization study shows that cyclin D2 and Mel-18 interact within the nucleus. To determine whether Mel-18 affects cyclin D2 activity, we blocked Mel-18 expression using an anti-sense strand system in cyclin D2 over-expressing cells. The results indicate that cells with reduced Mel-18 expression levels show more proliferative activity than the controls. These findings are the first report that Mel-18 directly interacts with cyclin D2 and may inhibit cyclin D2 activity.