Dimerization of the Polycomb-group protein Mel-18 is regulated by PKC phosphorylation

The Polycomb-group (Pc-G) gene products form complexes via protein-protein interactions and maintain the transcriptional repression of genes involved in embryogenesis, cell cycle, and tumorigenesis. Previously,we ha e shown that mouse Me1-18, a Pc-G protein, has tumor suppressor gene-like activity and negatively regulates transcription. Here, we show in vitro by pull-do n assays and in vivo in transiently transfected COS-7 cells that Me1-18 forms homodimers. Deletion analysis revealed that the N-terminal RING-finger and alpha-helix domains are required for homodimer formation. In addition. we demonstrated that Me1-18 homo-dimerization is regulated by protein kinase C (PKC) and protein phosphatases. such that dephosphorylated Me1-18 is able to homo-dimerize. These results suggest that the stoichiometry and/or equilibrium of subunits of the class 11 Polycomb complex containing Me1-18 might be regulated by changes in phosphorylation status via the PKC signaling pathway. (C) 2002 Elssevier Science (USA). All rights reserved.