SPIN1 promotes tumorigenesis by blocking the uL18-MDM2-p53 pathway
| Autor: | Bo Cao, Hua Lu, Shelya X. Zeng, Ziling Fang, Jianping Xiong, Kevin D Plummer, Tao Liu, Jun Deng, Peng Liao, Jun-Ming Liao |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0303 health sciences
Cell growth Nucleolus Cancer Biology medicine.disease medicine.disease_cause Molecular biology 3. Good health Cell biology 03 medical and health sciences 0302 clinical medicine Apoptosis 030220 oncology & carcinogenesis Cancer cell biology.protein medicine Mdm2 Carcinogenesis Clonogenic assay 030304 developmental biology |
| DOI: | 10.1101/177881 |
| Popis: | Ribosomal proteins (RPs) play important roles in modulating the MDM2-p53 pathway. However, less is known about the upstream regulators of the RPs. Here we identify SPIN1 (Spindlin 1) as a novel binding partner of human RPL5/uL18 that is important for this pathway. SPIN1 ablation activates p53, suppresses cell growth, reduces clonogenic ability, and induces apoptosis of cancer cells by sequestering uL18 in the nucleolus, preventing it from interacting with MDM2, and thereby alleviating uL18-mediated inhibition of MDM2 ubiquitin ligase activity towards p53. SPIN1 deficiency increases ribosome-free uL18 and uL5 (human RPL11), which are required for SPIN1 depletion-induced p53 activation. Analysis of cancer genomic databases suggests that SPIN1 is highly expressed in several human cancers, and its overexpression is positively correlated with poor prognosis in cancer patients. Altogether, our findings reveal that the oncogenic property of SPIN1 is highly attributed to its negative regulation of uL18, leading to p53 inactivation. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|