| Institution: | 1. Cancer Institute, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China;2. Department of Radiation Oncology, Fudan University, Shanghai Cancer Center, Fudan University, Shanghai 200032, China;1. The Affiliated Tumor Hospital of Xinjiang Medical University, Xinjiang Uygur Autonomous Region, 830000, Urumqi, China;1. Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520, USA;2. Department of Chemistry, Yale University, New Haven, CT 06520, USA;1. Department of Biochemistry and Molecular Biology, College of Life Sciences, Key Laboratory of Bioactive Materials of Ministry of Education, State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin, China;2. Institute for Cardiovascular Science & Department of Cardiovascular Surgery of the First Affiliated Hospital, Medical College, Soochow University, Suzhou, China;3. Department of Pharmacological Sciences, Key Laboratory of Metabolism and Regulation for Major Diseases of Anhui Higher Education Institutes, College of Food and Biological Engineering, Hefei University of Technology, Hefei, China;1. Department of Biomedical Engineering, Tulane University, New Orleans, LA 70118, USA;2. Biostatistics Program, School of Public Health, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA;3. Center for Bioinformatics and Genomics, Department of Global Biostatistics and Data Science, Tulane University, New Orleans, LA 70112, USA;4. Department of Electrical and Computer Engineering, The University of New Mexico, Albuquerque, NM 87131, USA |
| Abstract: | The F-box protein is the substrate recognition subunit of SCF (SKP1/CUL1/F-box) E3 ubiquitin ligase complex, a multicomponent RING-type E3 ligase involved in the regulation of numerous cellular processes by targeting critical regulatory proteins for ubiquitination. However, whether and how F-box proteins are regulated is largely unknown. Here we report that FBXO28, a poorly characterized F-box protein, is a novel substrate of SCF E3 ligase. Pharmaceutical or genetic inhibition of neddylation pathway that is required for the activation of SCF stabilizes FBXO28 and prolongs its half-life. Meanwhile, FBXO28 is subjected to ubiquitination and cullin1-based SCF complex promotes FBXO28 degradation. Moreover, deletion of F-box domain stabilizes FBXO28 and knockdown of endogenous FBXO28 strongly upregulates exogenous FBXO28 expression. Taken together, these data reveal that SCFFBXO28 is the E3 ligase responsible for the self-ubiquitination and proteasomal degradation of FBXO28, providing a new clue for the upstream signaling regulation for F-box proteins. |
