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

Oncotarget
Shujun GaoMong-Hong Lee

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.

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Citations

Apr 1, 2020·British Journal of Cancer·Baifu QinMong-Hong Lee
Jun 1, 2016·IUBMB Life·Jean-Pierre ObeidJimmy El Hokayem
Jul 18, 2019·Cancer Biology & Therapy·Jiaqi ShiYanqiao Zhang
Dec 30, 2017·International Journal of Molecular Medicine·Rui WangZhengxia Wu
Apr 10, 2019·Anti-cancer Agents in Medicinal Chemistry·Zun MaoDong-Sheng Pei
Jun 3, 2021·Cancers·Ranadip MandalKlaus Strebhardt

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Datasets Mentioned

BETA
GSE6783

Methods Mentioned

BETA
co-immunoprecipitation
ubiquitination
flow cytometry
flow
transfection
immunoprecipitation
electrophoresis

Software Mentioned

Flow Cytometry Analysis
imageJ

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