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Vol. 16, Issue 11, 5433-5444, November 2005

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TRAF7 Sequesters c-Myb to the Cytoplasm by Stimulating Its Sumoylation

Yutaka Morita ^* , Chie Kanei-Ishii ^*, Teruaki Nomura ^* , and Shunsuke Ishii ^* 

^* Laboratory of Molecular Genetics, RIKEN Tsukuba Institute, Tsukuba, Ibaraki 305-0074, Japan; Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Ibaraki 305-8577, Japan

Submitted August 8, 2005; Revised August 29, 2005; Accepted September 2, 2005
Monitoring Editor: William Tansey

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.

Abbreviations used: c-Myb, c-myb proto-oncogene product; DBD, DNA-binding domain; NLK, Nemo-like kinase; NPCs, nuclear pore complexes; NRD, negative regulatory domain; PIAS, protein inhibitors of activated STATs; SUMO, small ubiquitin-related modifier.

The online version of this article contains supplemental material at MBC Online (http://www.molbiolcell.org).

Address correspondence to: Shunsuke Ishii (sishii{at}rtc.riken.jp).

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