TRIM6 interacts with Myc and maintains the pluripotency of mouse embryonic stem cells.
The proto-oncogene product Myc is a master regulator of cell proliferation through its specific binding to the E-box motif in genomic DNA. It has been reported that Myc has an important role in the proliferation and maintenance of the pluripotency of embryonic stem (ES) cells and that the transcriptional activity of Myc is regulated by several post-translational modifications, including ubiquitination. In this study, we showed that tripartite motif containing 6 (TRIM6), one of the TRIM family ubiquitin ligases, was selectively expressed in ES cells and interacted with Myc followed by attenuation of the transcriptional activity of Myc. Knockdown of TRIM6 in ES cells enhanced the transcriptional activity of Myc and repressed expression of NANOG, resulting in the promotion of ES cell differentiation. These findings indicate that TRIM6 regulates the transcriptional activity of Myc during the maintenance of ES cell pluripotency, suggesting that TRIM6 functions as a novel regulator for Myc-mediated transcription in ES cells.
Department of Biochemistry, Hokkaido University Graduate School of Medicine, Kita15, Nishi7, Kita-ku, Sapporo, Hokkaido 060-8638,  Japan.
Tomonobu
T
Sato
Fumihiko
F
Okumura
Tadashi
T
Ariga
Shigetsugu
S
Hatakeyama
D000595:Amino Acid Sequence; D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D053595:Embryonic Stem Cells / Q000166:cytology / Q000201:enzymology*; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D055785:Gene Knockdown Techniques / Q000379:methods; D057809:HEK293 Cells; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D041681:NIH 3T3 Cells; D000071317:Nanog Homeobox Protein; D010766:Phosphorylation / Q000502:physiology; D039904:Pluripotent Stem Cells / Q000166:cytology / Q000201:enzymology*; D000090063:Proto-Oncogene Mas; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D014158:Transcription, Genetic / Q000502:physiology; D000070584:Tripartite Motif Proteins; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism*; D054875:Ubiquitination / Q000502:physiology
D018398:Homeodomain Proteins; C000715470:MAS1 protein, human; C489428:Myc protein, mouse; D000071317:Nanog Homeobox Protein; C475540:Nanog protein, mouse; D000090063:Proto-Oncogene Mas; D016271:Proto-Oncogene Proteins c-myc; D000070584:Tripartite Motif Proteins; C578076:TRIM6 protein, mouse; D044767:Ubiquitin-Protein Ligases