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 have shown that mouse Mel-18, a Pc-G protein, has tumor suppressor gene-like activity and negatively regulates transcription. Here, we show in vitro by pull-down assays and in vivo in transiently transfected COS-7 cells that Mel-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 Mel-18 homo-dimerization is regulated by protein kinase C (PKC) and protein phosphatases, such that dephosphorylated Mel-18 is able to homo-dimerize. These results suggest that the stoichiometry and/or equilibrium of subunits of the class II Polycomb complex containing Mel-18 might be regulated by changes in phosphorylation status via the PKC signaling pathway.
Fujisaki
Seiji
S
Department of Immunology, Graduate School of Science, Hiroshima University, 1-2-3, Kasumi, Minami-ku, Japan.
Ninomiya
Yuichi
Y
Ishihara
Hiroto
H
Miyazaki
Masaki
M
Kanno
Rieko
R
Asahara
Toshimasa
T
Kanno
Masamoto
M
D020816:Amino Acid Motifs; D000818:Animals; D019556:COS Cells; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D019281:Dimerization; D051379:Mice; D010766:Phosphorylation; D063150:Polycomb Repressive Complex 1; D011493:Protein Kinase C / Q000378:metabolism*; D020836:Protein Structure, Quaternary; D021122:Protein Subunits; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D014162:Transfection; D016335:Zinc Fingers
D004268:DNA-Binding Proteins; C066476:Pcgf6 protein, mouse; D021122:Protein Subunits; D011994:Recombinant Proteins; D063150:Polycomb Repressive Complex 1; D011493:Protein Kinase C