title: COP9 signalosome subunit 6 (CSN6) regulates E6AP/UBE3A in cervical cancer.
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.
authors: Obstetrics and Gynecology Hospital Fudan University, Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Shanghai 200011, China.|Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
authors: Shujun
authors: S
authors: Gao
authors: Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.|Department of Colorectal Surgery, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou 510655, China.
authors: Lekun
authors: L
authors: Fang
authors: Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
authors: Liem Minh
authors: LM
authors: Phan
authors: Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
authors: Aiham
authors: A
authors: Qdaisat
authors: Department of Endocrine Neoplasia and Hormonal Disorders, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.|Department of Emergency Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
authors: Sai-Ching J
authors: SC
authors: Yeung
authors: Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.|Department of Colorectal Surgery, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou 510655, China.|Program in Cancer Biology, The University of Texas Graduate School of Biomedical Sciences at Houston, Houston, TX 77030, USA.|Program in Genes and Development, The University of Texas Graduate School of Biomedical Sciences at Houston, Houston, TX 77030, USA.
authors: Mong-Hong
authors: MH
authors: Lee
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000818:Animals; D000075686:COP9 Signalosome Complex; D002469:Cell Separation; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D005260:Female; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D006367:HeLa Cells; D006801:Humans; D015151:Immunoblotting; D047468:Immunoprecipitation; D051379:Mice; D008819:Mice, Nude; D030361:Papillomavirus Infections / Q000150:complications*; D016133:Polymerase Chain Reaction; D034741:RNA, Small Interfering; D014162:Transfection; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000473:pathology* / Q000821:virology; D023041:Xenograft Model Antitumor Assays
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C470634:COPS6 protein, human; D034741:RNA, Small Interfering; C471639:UBE3A protein, human; D044767:Ubiquitin-Protein Ligases; D000075686:COP9 Signalosome Complex
keywords: CSN6; E6AP; cervical cancer; p53; ubiquitination