Data for: HPV upregulates MARCHF8 ubiquitin ligase and inhibits apoptosis by degrading the death receptors in head and neck cancer

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.