COP9 signalosome subunit 6 (CSN6) regulates E6AP/UBE3A in cervical cancer.

Cervical cancer is one of the leading causes of cancer death in women. Human papillomaviruses (HPVs) are the major cause in almost 99.7% of cervical cancer. E6 oncoprotein of HPV and E6-associated protein (E6AP) are critical in causing p53 degradation and malignancy. Understanding the E6AP regulation is critical to develop ...
treating strategy for cervical cancer patients. The COP9 signalosome subunit 6 (CSN6) is involved in ubiquitin-mediated protein degradation. We found that both CSN6 and E6AP are overexpressed in cervical cancer. We characterized that CSN6 associated with E6AP and stabilized E6AP expression by reducing E6AP poly-ubiquitination, thereby regulating p53 activity in cell proliferation and apoptosis. Mechanistic studies revealed that CSN6-E6AP axis can be regulated by EGF/Akt signaling. Furthermore, inhibition of CSN6-E6AP axis hinders cervical cancer growth in mice. Taken together, our results indicate that CSN6 is a positive regulator of E6AP and is important for cervical cancer development.
Mesh Terms:
Adaptor Proteins, Signal Transducing, Animals, Cell Separation, Cell Transformation, Neoplastic, Female, Flow Cytometry, Gene Expression Regulation, Neoplastic, HeLa Cells, Humans, Immunoblotting, Immunoprecipitation, Mice, Mice, Nude, Papillomavirus Infections, Polymerase Chain Reaction, RNA, Small Interfering, Transfection, Ubiquitin-Protein Ligases, Uterine Cervical Neoplasms, Xenograft Model Antitumor Assays
Oncotarget
Date: Sep. 29, 2015
Download Curated Data For This Publication
205986
Switch View:
  • Interactions 2
  • PTM Genes 1