HGNC Approved Gene Symbol: RNF208Cytogenetic location: 9q34.3 Genomic coordinates (GRCh38): 9:137,220,258-137,223,407 (from NCBI)▼ DescriptionRNF208 is an es...
HGNC Approved Gene Symbol: RNF208
Cytogenetic location: 9q34.3 Genomic coordinates (GRCh38): 9:137,220,258-137,223,407 (from NCBI)
RNF208 is an estrogen-induced ubiquitin E3 ligase that mediates degradation of soluble vimentin (VIM; 193060) (Pang et al., 2019).
▼ Cloning and Expression
Using RNA sequencing, Pang et al. (2019) identified RNF208 based on its lower expression in triple-negative human breast cancer (TNBC; see 114480) cells compared with luminal breast cancer cells. The RNF208 protein contains a RING domain.
▼ Gene Structure
Pang et al. (2019) determined that the RNF208 promoter contains 4 putative estrogen-responsive elements (EREs).
Gross (2020) mapped the RNF208 gene to chromosome 9q34.3 based on an alignment of the RNF208 sequence (GenBank BC016958) with the genomic sequence (GRCh38).
▼ Gene Function
Using RT-PCR, immunoblot, microarray, and immunohistochemical analyses, Pang et al. (2019) confirmed that RNF208 expression was lower in human TNBC compared with luminal breast cancer. In breast cancer patients, low RNF208 expression was associated with a shorter time to relapse and poor relapse-free survival. Pang et al. (2019) determined that RNF208 expression positively correlated with ESR1 (133430) expression and was induced by estradiol (E2). Mutation and chromatin immunoprecipitation analyses showed that ESR1 bound the EREs in the RNF208 promoter to induce RNF208 expression. Overexpression of RNF208 decreased tumor volume of TNBC cells and was associated with decreased cell proliferation and increased cell death. RNF208 overexpression also decreased cell migration in TNBC cells and reduced metastasis in a mouse model of lung cancer. However, knockdown or knockout of RNF208 did not induce cancer progression or migration, suggesting that RNF208 acts as a tumor suppressor. Crosslinking and immunoprecipitation showed that RNF208 bound the head domain of soluble vimentin. Expression of RNF208 and vimentin was inversely correlated in breast cancer samples, and RNF208 overexpression decreased vimentin protein expression and stability and increased lys27-linked polyubiquitination of vimentin at lys97. Interaction with and polyubiquitination of vimentin relied on an intact RING finger domain of RNF208 and phosphorylation of ser39 in the head domain of soluble vimentin.