Myc and Skp2 overexpression promotes p27 ubiquitination and degradation in Ewing Sarcoma - PubMed
2 days ago
- #Ewing Sarcoma
- #Myc and Skp2
- #p27 ubiquitination
- Myc and Skp2 overexpression promotes p27 ubiquitination and degradation in Ewing Sarcoma.
- Ewing sarcoma remains highly malignant and difficult to control with current treatments.
- Comprehensive mRNA expression analysis identified elevated Myc and Skp2 in all five Ewing sarcoma cell lines examined.
- siRNA knockdown of Myc and Skp2 led to reduced cell growth and G1 arrest.
- Knockdown cells showed decreased CDK2 activity, increased p27 expression, and reduced cyclin E (CCNE) levels.
- The CCNE/CDK2 complex enhanced p27 phosphorylation at Thr187, accelerating its degradation via Skp2-mediated ubiquitination.
- The CCNE/CDK2 complex also promoted Rb phosphorylation at Ser807/808, involved in E2F1 activation.
- Findings suggest new therapeutic strategies for Ewing sarcoma, addressing the lack of effective targeted therapies.