A08
The role of RNF213 and its variants in lung tumor
Project Summary
Ring finger protein 213 (RNF213) contains an active E3 ligase domain in addition to a AAA+ ATPase domain and was reported to be expressed in different splice isoforms. RNF213 plays a role in cell intrinsic inflammatory signaling, and its ubiquitylation function is also essential to fine-tune pathways, such as AKT, nF-κb or WNT, which are well-studied drivers of cancer and frequently deregulated in non-small cell lung cancer (NSCLC). The function of RNF213 and its role in the control of these pathways or novel signaling cascades remains unclear but may hold the key to modulate tumor-driving pathways. In this project, we aim at defining the molecular and cellular function of RNF213 and its variants, concerning its substrates and functional dependencies in tumor and tumor-associated cells. Focusing on the role of RNF213 variants in lung cancer and the differences of their activity during cell-intrinsic inflammation, vascularization and antigen presentation, we identify novel cancer vulnerabilities in RNF213-dependent ubiquitylation pathways that may be targeted modulate lung cancer progression.
