title: Rabring7 degrades c-Myc through complex formation with MM-1.
abstract: We have reported that a novel c-Myc-binding protein, MM-1, repressed E-box-dependent transcription and transforming activities of c-Myc and 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. MM-1 also binds to the ubiquitin-proteasome system, leading to degradation of c-Myc. In this study, we identified Rabring7, a Rab7-binding and RING finger-containing protein, as an MM-1-binding protein, and we found that Rabring7 mono-ubiquitinated MM-1 in the cytoplasm without degradation of MM-1. Rabring7 was also found to bind to c-Myc and to ubiquitinate c-Myc in a threonine 58-dependent manner. When c-Myc was co-transfected with MM-1 and Rabring7, c-Myc was degraded. Furthermore, it was found that c-Myc was stabilized in MM-1-knockdown cells even when Rabring7 was transfected and that Rabring7 was bound to and co-localized with MM-1 and c-Myc after MM-1 and Rabring7 had been translocated from the cytoplasm to the nucleus. These results suggest that Rabring7 stimulates c-Myc degradation via mono-ubiquitination of MM-1.
authors: Graduate School of Agriculture, Hokkaido University, Sapporo, Japan.
authors: Rina
authors: R
authors: Narita
authors: Hirotake
authors: H
authors: Kitaura
authors: Ayako
authors: A
authors: Torii
authors: Erika
authors: E
authors: Tashiro
authors: Makoto
authors: M
authors: Miyazawa
authors: Hiroyoshi
authors: H
authors: Ariga
authors: Sanae M M
authors: SM
authors: Iguchi-Ariga
mesh_terms: D002460:Cell Line; D049109:Cell Proliferation; D006801:Humans; D011485:Protein Binding; D055550:Protein Stability; D059748:Proteolysis; D016271:Proto-Oncogene Proteins c-myc / Q000737:chemistry / Q000378:metabolism*; D012097:Repressor Proteins / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*; D054875:Ubiquitination
chemical_list: C115636:PFDN5 protein, human; D016271:Proto-Oncogene Proteins c-myc; D012097:Repressor Proteins; C506934:RNF115 protein, human; D044767:Ubiquitin-Protein Ligases