CacyBP/SIP protein reduces p53 stability by enhancing Mdm2 activity in p53 mutant glioma cells
| Autor: | Shiquan Wang, Fengyuan Qian, Hengliang Shi, Tianjin Tang, Bin Wang, Lei Wang |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Cancer Research
biology Chemistry Protein Stability Mutant Calcium-Binding Proteins Proto-Oncogene Proteins c-mdm2 Glioma Glioma cell medicine.disease Cell biology Ubiquitin ligase Oncology Ubiquitin Cell culture Cell Line Tumor biology.protein medicine Mdm2 Humans Cacybp sip Tumor Suppressor Protein p53 Cell Proliferation |
| Zdroj: | Neoplasma. 68(1) |
| ISSN: | 0028-2685 |
| Popis: | Our previous studies have illustrated that CacyBP/SIP (Calcyclin-binding protein or Siah-1-interacting protein) promoted the proliferation of glioma cells. However, the possible mechanism still needs to be clarified. In the current study, we aimed to uncover the potential mechanism of CacyBP/SIP in regulating glioma cell proliferation. We found that CacyBP/SIP decreased the protein level of p53, but not the mRNA level of p53 in p53 mutant U251 cell line, whereas, in p53 wild-type U87 cell line, CacyBP/SIP neither promoted its proliferation nor regulated the changes of p53 protein. Further investigation indicated that CacyBP/SIP interacted with p53 and Mdm2 (Mouse double minute 2) to promote p53 ubiquitination and subsequent proteasome-mediated degradation in U251. Moreover, in the presence of Mdm2, CacyBP/SIP boosted the ubiquitination of p53 in a dose-dependent manner. On the contrary, inhibition of Mdm2 activity significantly increased the stability of p53. Finally, we found that the protein level of CacyBP/SIP and p53 is inversely correlated in p53 mutant human glioma tissues. These observations suggest an underlying mechanism that CacyBP/SIP promotes the degradation of p53 by enhancing Mdm2 E3 ligase activity, which reveals a novel pathway for the regulation of mutant p53 and provides a new therapeutic approach to target the CacyBP/SIP-induced glioma cell proliferation. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|