MM-1 facilitates degradation of c-Myc by recruiting proteasome and a novel ubiquitin E3 ligase

  • Authors:
    • Yumiko Kimura
    • Arisa Nagao
    • Yuko Fujioka
    • Akiko Satou
    • Takahiro Taira
    • Sanae M.M. Iguchi-Ariga
    • Hiroyoshi Ariga
  • View Affiliations

  • Published online on: October 1, 2007     https://doi.org/10.3892/ijo.31.4.829
  • Pages: 829-836
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Abstract

We have reported that a novel c-Myc-binding protein, MM-1, repressed the E-box-dependent transcription activity of c-Myc by recruiting the HDAC1 complex via TIF1β/KAP1, a transcriptional corepressor. We have also reported that a mutation of A157R in MM-1, which is often observed in patients with leukemia or lymphoma, abrogated all of the repressive activities of MM-1 toward c-Myc, indicating that MM-1 is a novel tumor suppressor. In this study, we found that MM-1 was bound to a component of proteasome and stimulated degradation of c-Myc in human cells. Knockdown of endogenous MM-1 in human HeLa cells by introduction of siRNA against MM-1 stabilized the endogenous c-Myc. To identify proteins that participate in c-Myc degradation by MM-1, in vivo and in vitro binding assays were carried out. The results showed that MM-1 directly bound to Rpt3, a subunit of 26S proteasome, and that c-Myc directly bound to Skp2, which recruited ElonginC, ElonginB and Cullin2, thereby forming a novel ubiquitin E3 ligase. Knockdown of endogenous Cullin2 stabilized the endogenous c-Myc. Thus, MM-1 is a factor that connects c-Myc to the ubiquitin E3 ligase and the proteasome.

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October 2007
Volume 31 Issue 4

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Kimura Y, Nagao A, Fujioka Y, Satou A, Taira T, Iguchi-Ariga SM and Ariga H: MM-1 facilitates degradation of c-Myc by recruiting proteasome and a novel ubiquitin E3 ligase. Int J Oncol 31: 829-836, 2007.
APA
Kimura, Y., Nagao, A., Fujioka, Y., Satou, A., Taira, T., Iguchi-Ariga, S.M., & Ariga, H. (2007). MM-1 facilitates degradation of c-Myc by recruiting proteasome and a novel ubiquitin E3 ligase. International Journal of Oncology, 31, 829-836. https://doi.org/10.3892/ijo.31.4.829
MLA
Kimura, Y., Nagao, A., Fujioka, Y., Satou, A., Taira, T., Iguchi-Ariga, S. M., Ariga, H."MM-1 facilitates degradation of c-Myc by recruiting proteasome and a novel ubiquitin E3 ligase". International Journal of Oncology 31.4 (2007): 829-836.
Chicago
Kimura, Y., Nagao, A., Fujioka, Y., Satou, A., Taira, T., Iguchi-Ariga, S. M., Ariga, H."MM-1 facilitates degradation of c-Myc by recruiting proteasome and a novel ubiquitin E3 ligase". International Journal of Oncology 31, no. 4 (2007): 829-836. https://doi.org/10.3892/ijo.31.4.829