Abstract
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.
Original language | English (US) |
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Pages (from-to) | 28026-28041 |
Number of pages | 16 |
Journal | Oncotarget |
Volume | 6 |
Issue number | 29 |
DOIs | |
State | Published - 2015 |
Keywords
- 53
- CSN6
- Cervical cancer
- E6AP
- Ubiquitination
ASJC Scopus subject areas
- Oncology
MD Anderson CCSG core facilities
- Functional Genomics Core