TRAF7 sequesters c-Myb to the cytoplasm by stimulating its sumoylation.
Small ubiquitin-related modifiers (SUMOs) are proteins that are posttranslationally conjugated to diverse proteins. The c-myb proto-oncogene product (c-Myb) regulates proliferation and differentiation of hematopoietic cells. PIASy is the only known SUMO E3 ligase for c-Myb. Here, we report that TRAF7 binds to c-Myb and stimulates its sumoylation. TRAF7 bound to the DNA-binding domain of c-Myb via its WD40 repeats. TRAF7 has an E3 ubiquitin ligase activity for self-ubiquitination, but TRAF7 also stimulated the sumoylation of c-Myb at Lys-523 and Lys-499, which are the same sites as those used for PIASy-induced sumoylation. TRAF7 inhibited trans-activation induced by wild-type c-Myb, but not by the sumoylation site mutant of c-Myb. The expression of both c-myb and TRAF7 was down-regulated during differentiation of M1 cells. Endogenous TRAF7 localized to both the cytoplasm and nucleus of M1 cells. Consistent with this, significant amounts of sumoylated c-Myb were found in the cytoplasm of M1 cells, whereas nonsumoylated c-Myb was found predominantly in the nucleus. Overexpressed TRAF7 was localized in the cytoplasm of CV-1 cells, and sequestered c-Myb and SUMO1 in the cytosol, whereas PIASy was localized in the nucleus. Thus, TRAF7 negatively regulates c-Myb activity by sequestering c-Myb to the cytosol via sumoylation.
Morita
Yutaka
Y
Laboratory of Molecular Genetics, RIKEN Tsukuba Institute, Tsukuba, Ibaraki 305-0074, Japan.
Kanei-Ishii
Chie
C
Nomura
Teruaki
T
Ishii
Shunsuke
S
D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D045744:Cell Line, Tumor; D003593:Cytoplasm / Q000378:metabolism; D008025:Ligases / Q000378:metabolism; D051379:Mice; D020598:Proto-Oncogene Proteins c-myb / Q000378:metabolism*; D025842:SUMO-1 Protein / Q000378:metabolism*; D015533:Transcriptional Activation / Q000235:genetics; D047988:Tumor Necrosis Factor Receptor-Associated Peptides and Proteins / Q000378:metabolism* / Q000502:physiology*
D002352:Carrier Proteins; D020598:Proto-Oncogene Proteins c-myb; D025842:SUMO-1 Protein; C486461:Traf7 protein, mouse; D047988:Tumor Necrosis Factor Receptor-Associated Peptides and Proteins; D008025:Ligases