한빛사논문
- 조회542
Mohamed I Khalil 1 2, Canchai Yang 1, Lexi Vu 1, Smriti Chadha 1, Harrison Nabors 1, Craig Welbon 3, Claire D James 4, Iain M Morgan 4, William C Spanos 3, Dohun Pyeon 1
1Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, Michigan, United States of America.
2Department of Molecular Biology, National Research Centre, El-Buhouth St., Cairo, Egypt.
3Cancer Biology and Immunotherapies Group, Sanford Research, Sioux Falls, South Dakota, United States of America.
4Philips Institute for Oral Health Research, School of Dentistry, Virginia Commonwealth University, Richmond, Virginia, United States of America.
Corresponding author: Dohun Pyeon
Abstract
The membrane-associated RING-CH-type finger ubiquitin ligase MARCHF8 is a human homolog of the viral ubiquitin ligases Kaposi’s sarcoma herpesvirus K3 and K5 that promote host immune evasion. Previous studies have shown that MARCHF8 ubiquitinates several immune receptors, such as the major histocompatibility complex II and CD86. While human papillomavirus (HPV) does not encode any ubiquitin ligase, the viral oncoproteins E6 and E7 are known to regulate host ubiquitin ligases. Here, we report that MARCHF8 expression is upregulated in HPV-positive head and neck cancer (HNC) patients but not in HPV-negative HNC patients compared to normal individuals. The MARCHF8 promoter is highly activated by HPV oncoprotein E6-induced MYC/MAX transcriptional activation. The knockdown of MARCHF8 expression in human HPV-positive HNC cells restores cell surface expression of the tumor necrosis factor receptor superfamily (TNFRSF) death receptors, FAS, TRAIL-R1, and TRAIL-R2, and enhances apoptosis. MARCHF8 protein directly interacts with and ubiquitinates the TNFRSF death receptors. Further, MARCHF8 knockout in mouse oral cancer cells expressing HPV16 E6 and E7 augments cancer cell apoptosis and suppresses tumor growth in vivo. Our findings suggest that HPV inhibits host cell apoptosis by upregulating MARCHF8 and degrading TNFRSF death receptors in HPV-positive HNC cells.
논문정보
- Research article
- 2023년 03월 (BRIC 등록일 2023-04-19)
- 국외 연구진
- 의약학 > 종양의학
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