Disease relevance of RNF41

• Loss of Nrdp1 Enhances ErbB2/ErbB3-Dependent Breast Tumor Cell Growth [1].

High impact information on RNF41

• In the presence of an exogenous E2, UbcH5c, purified Nrdp1 catalyzes BRUCE ubiquitination [2].
• Nrdp1/FLRF is a RING finger-containing ubiquitin ligase that catalyzes degradation of the EGF receptor family member, ErbB3 [2].
• Thus, BRUCE normally inhibits apoptosis, and Nrdp1 can be important in the initiation of apoptosis by catalyzing ubiquitination and degradation of BRUCE [2].
• Our observations suggest that Nrdp1 may act to regulate steady-state cell surface neuregulin receptor levels, thereby influencing the efficiency of neuregulin signaling [3].
• Northern blotting reveals ubiquitous distribution of Nrdp1 in human adult tissues, but message is particularly prominent in heart, brain, and skeletal muscle [3].

Biological context of RNF41

• The USP8 rhodanese and catalytic domains mediated Nrdp1 binding [4].
• Furthermore, decreasing BRUCE content by RNA interference or overexpression of Nrdp1 promotes apoptosis [2].
• The structure of the rhodanese domain, determined in complex with the E3 ligase NRDP1, reveals the canonical rhodanese fold but with a distorted primordial active site [5].
• A consensus sequence of this loop is found in other NRDP1 targets, suggesting a common mode of interaction [5].
• Amino-terminal Dimerization, NRDP1-Rhodanese Interaction, and Inhibited Catalytic Domain Conformation of the Ubiquitin-specific Protease 8 (USP8) [5].

Associations of RNF41 with chemical compounds

• RING finger ubiquitin-protein isopeptide ligase Nrdp1/FLRF regulates parkin stability and activity [6].
• Structure-based mutagenesis of the substrate-recognition domain of Nrdp1/FLRF identifies the binding site for the receptor tyrosine kinase ErbB3 [7].

Physical interactions of RNF41

• Furthermore, we have used site-directed mutagenesis to map regions of the Nrdp1 surface that are important for interacting with ErbB3 and mediating its degradation in transfected cells [7].

Regulatory relationships of RNF41

• In vivo, overexpression of Nrdp1 promotes ubiquitination and proteasomal degradation of BRUCE [2].
• In contrast, either Nrdp1 knockdown or the overexpression of a dominant-negative form enhances ErbB3 levels and cellular proliferation [1].

Other interactions of RNF41

• We have named this protein Nrdp1 for neuregulin receptor degradation protein-1 [3].

Analytical, diagnostic and therapeutic context of RNF41

• Using affinity chromatography, we identified the deubiquitinating enzyme USP8 (also called Ubpy) as a protein that physically interacts with Nrdp1 [4].
• Nrdp1 belongs to the tripartite or RBCC (RING, B-box, coiled-coil) family of ubiquitin ligases in which the RING domain is responsible for ubiquitin ligation and a variable C-terminal region mediates substrate recognition [7].

References