LAUSR

F-box proteins are major components of the SCF (SKP1-CUL1-F-box) E3 ubiquitin ligases as they are responsible for substrate recognition. In this complex, F-box proteins bind to SKP1 through the F-box motif to bring the ubiquitination machinery and mediate protein ubiquitination of the substrates. So far, 69 F-box proteins are identified in humans, and they fall into 3 families depending on their substrate recognition domains: FBXLs (Leucine-Rich Repeats or LRR), FBXWs (WD repeats) and FBXOs (Other domains). FBXL16 is a poorly studied F-box protein which consists of an N-terminal Proline-rich domain, an F-box motif and a C-terminal domain of Leucine-rich repeats. FBXL16 was first identified as a transcriptional target of E2F1 (Sato et al, 2010) and was then showed as a binding partner of PP2A (Protein Phosphatase 2A) and as a regulator of its phosphatase activity (Honarpour et al, 2014). Interestingly, FBXL16 was shown to be overexpressed in a number of cancers, particularly invasive breast carcinoma (Oncomine) indicating that FBXL16 may play important roles in cancers. In this study, by both knockdown and overexpression experiments, we found that FBXL16 promotes cancer cell migration. To our surprise, we observed that knockdown of FBXL16 in cancer cells resulted in a strong decrease of c-myc protein level. Importantly, we also found that FBXL16 binds to and stabilizes c-myc protein. Mechanistically, FBXL16 overexpression decreased c-myc protein ubiquitination. Taken together, our study demonstrates a positive role of FBXL16 in regulating c-myc protein stability by inhibiting its ubiquitination. Citation Format: Marion Morel, Weiwen Long. The F-box protein FBXL16 regulates the stability of c-myc oncoprotein [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3462.