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.

Nuclear functions of prefoldin

“…It favours c-Myc degradation by recruiting the ubiquitin ligase Skp2–ElonginC–ElonginB–Cullin2 complex, and driving it to the proteasome via the 26S subunit Rpt3 [54] (figure 3 b ). The monoubiquitination of PFDN5 by Rabring7, a Rab7-binding and RING finger-containing protein, stimulates this second role of PFDN5 in the control of c-Myc [55] (figure 3 b ). In addition, PFDN5 and the Egr-1 repressor bind and downregulate the promoter of the wnt4 gene.…”

Expansion and Diversification of BTL Ring-H2 Ubiquitin Ligases in Angiosperms: Putative Rabring7/BCA2 Orthologs

“…It interacts with Tetherin, a membrane-anchored protein that retains HIV-1 particles during the final phase of viral replication, and promotes internalization and degradation of these particles [16]. It also has a role in the regulation of Epidermal Growth Factor Receptor (EGFR) trafficking for lysosomal degradation [17] and assists in the degradation of the proto-oncogene c-Myc through a complex with MM-1, which is a tumor suppressor that binds to the myc box II [18]. A Rabring7/BCA2-like protein is present in vertebrates.…”

Deubiquitinase ubiquitin‐specific protease 9X regulates the stability and function of E3 ubiquitin ligase ring finger protein 115 in breast cancer cells

“…For example, it was reported that RNF115 targets p21 for ubiquitin‐mediated degradation to promote breast cancer cell proliferation . In addition, RNF115 has been shown to stimulate ubiquitination and degradation of c‐Myc and epidermal growth factor receptor in other model systems . Interestingly, we found that depletion or overexpression of RNF115 does not affect USP9X protein abundance (Figure ).…”

“…13 In addition, RNF115 has been shown to stimulate ubiquitination and degradation of c-Myc and epidermal growth factor receptor in other model systems. 32,33 Interestingly, we found that depletion or overexpression of RNF115 does not affect USP9X protein abundance (Figure 2). In support of our findings, a recent study showed that SMURF1, a member of the Nedd4 family of HECT ubiquitin ligases, interacts with USP9X but this association does not lead to USP9X degradation.…”