Decreased serum dependence in the growth of NIH3T3 cells from the overexpression of human nuclear receptor-binding SET-domain-containing protein 1 (NSD1) or fission yeast su(var)3-9, enhancer-of-zeste, trithorax 2 (SET2).
Nuclear receptor-binding SET-domain-containing protein 1 (NSD1), a culprit gene for Sotos syndrome, contains a su(var)3-9, enhancer-of-zeste, trithorax (SET) domain that is responsible for histone methyltransferase activity and other domains such as plant homeodomain (PHD) and proline-tryptophan-tryptophan-proline (PWWP) involved in protein-protein interactions in the C-terminal half of NSD1. To elucidate the function of NSD1 on cell growth, we overexpressed NSD1 in NIH3T3 cells. Cells overexpressing NSD1 grew in the presence of 2% serum, whereas vector transfected cells did not. Overexpression of the C-terminal half of NSD1 but not the N-terminal half of NSD1 also produced cell growth under low serum concentration. Furthermore, overexpression in NIH3T3 of Schizosaccharomyces pombe SET2 which has a SET domain but not PHD or PWWP domains conferred the reduced serum dependence. Thus, the SET domain of NSD1 is involved in cell growth by modulating serum dependence.
Yamada-Okabe
Toshiko
T
Department of Human Genetics, Yokohama City University Graduate School of Medicine, Japan. t-okabe@star.sagami-wu.ac.jp
Matsumoto
Naomichi
N
D000595:Amino Acid Sequence; D000818:Animals; D049109:Cell Proliferation; D003470:Culture Media / Q000737:chemistry; D020869:Gene Expression Profiling; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase / Q000096:biosynthesis / Q000235:genetics* / Q000502:physiology; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics* / Q000502:physiology; D051379:Mice; D041681:NIH 3T3 Cells; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000502:physiology; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012568:Schizosaccharomyces / Q000378:metabolism; D029702:Schizosaccharomyces pombe Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000502:physiology; D017386:Sequence Homology, Amino Acid
D003470:Culture Media; D047908:Intracellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; D029702:Schizosaccharomyces pombe Proteins; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase; C113272:NSD1 protein, human; C527202:Set2 protein, S pombe