2024-03-29T01:16:07Zhttps://eprints.lib.hokudai.ac.jp/dspace-oai/requestoai:eprints.lib.hokudai.ac.jp:2115/537272022-11-17T02:08:08Zhdl_2115_20044hdl_2115_124MM-1 facilitates degradation of c-Myc by recruiting proteasome and a novel ubiquitin E3 ligase.Kimura, YumikoNagao, ArisaFujioka, YukoSatou, AkikoTaira, TakahiroIguchi-Ariga, Sanae M MAriga, Hiroyoshic-MycMM-1degradationubiquitin-proteasome system499Cullin Proteins/antagonists & inhibitorsCullin Proteins/geneticsCullin Proteins/metabolismHeLa CellsHumansProteasome Endopeptidase Complex/metabolismProto-Oncogene Proteins c-myc/geneticsProto-Oncogene Proteins c-myc/metabolismRNA, Small Interfering/pharmacologyRepressor Proteins/antagonists & inhibitorsRepressor Proteins/geneticsRepressor Proteins/metabolismS-Phase Kinase-Associated Proteins/geneticsS-Phase Kinase-Associated Proteins/metabolismTranscription Factors/geneticsTranscription Factors/metabolismTranscription, GeneticUbiquitin/metabolismUbiquitin-Protein Ligases/metabolismWe 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 TIF1beta/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.D.A. SpandidosJournal Articleapplication/pdfhttp://hdl.handle.net/2115/53727https://eprints.lib.hokudai.ac.jp/dspace/bitstream/2115/53727/1/178_Ariga_2007_Int_J_Onc.pdf1019-6439International journal of oncology3148298362007-10enginfo:pmid/17786314publisher