Melanoma antigen-A11 regulates substrate-specificity of Skp2-mediated protein degradation

作者：Su, Shifeng; Chen, Xiaoyu; Geng, Jiang; Minges, John T.; Grossman, Gail; Wilson, Elizabeth M.^*

来源：Molecular and Cellular Endocrinology, 2017, 439(C): 1-9.

DOI：10.1016/j.mce.2016.10.006

• Androgen receptor
• Melanoma antigen-A11
• MAGE-A11
• Skp2
• Cyclin A
• E2F1

Melanoma antigen-A11 (MACE-A11) is a proto-oncogene involved in androgen receptor signaling and androgen-dependent cell growth. In this report we provide evidence that MAGE-A11 interacts with Skp2 (S phase kinase-associated protein), the substrate recognition protein of the Skp1-Cullinl-F-box E3 ubiquitin ligase, and with Skp2 binding protein, cyclin A. A similar cyclin A binding motif in MACE-A11 and Skp2 was consistent with a competitive relationship between MACE-A11 and Skp2 in binding cyclin A. Skp2 inhibited MACE-A11 interaction with cyclin A. Differential effects of MACE-A11 on Skp2-mediated protein degradation were also revealed. MACE-A11 increased Skp2-mediated degradation of cyclin A and retinoblastoma-related protein p130. In contrast, MACE-A11 decreased Skp2-mediated degradation of E2F1 and Skp2 self-ubiquitination. Stabilization of E2F1 by MACE-A11 was associated with sequestration and inactivation of Skp2 through the formation of an E2F1-MACE-A11-Skp2 complex. We conclude that direct interactions of MACE-A11 with Skp2 and cyclin A regulate the substrate specificity of Skp2-mediated protein degradation.

• 出版日期2017-1-5
• 单位郑州大学; 同济大学; 南京医科大学