Membrane-associated RING-CH-type finger protein 8 (MARCHF8)

Membrane-associated RING-CH-type finger protein 8 (MARCHF8) is an E3 ubiquitin ligase member of the MARCH family, localized to cellular membranes, and is implicated as a key regulator in immune surveillance and viral infection. MARCHF8 directs the ubiquitination and subsequent lysosomal degradation of several immune receptors such as MHC-I, MHC-II, and co-stimulatory molecule CD86, thereby dampening antigen presentation and immune activation[2][3]. It also targets death receptors like FAS, TRAIL-R1, and TRAIL-R2, modulating apoptosis and survival, especially in cancers with viral etiology such as HPV-associated head and neck carcinoma[1][2]. MARCHF8 further participates in direct antiviral restriction by ubiquitinating viral glycoproteins including those from HIV, influenza, and others, promoting their degradation and impeding virion production and release[3]. In tumors, particularly HPV-positive, MARCHF8 upregulation promotes tumor growth by facilitating viral oncoprotein stability and suppressing apoptosis[1][2]. MARCHF8 expression is associated with poor prognosis in several malignant contexts, making it a potential, though challenging, therapeutic target for oncology and antiviral therapy[2][3].

Other names

E3 ubiquitin-protein ligase MARCHF8MARCH8MIRRNF178c-MIRMARCH-VIIICMIRCellular modulator of immune recognitionMembrane-associated ring finger protein 8Membrane-associated RING-CH protein VIIIRING finger protein 178RING-type E3 ubiquitin transferase MARCHF8

Ubiquitinates and induces degradation of immune receptors (e.g., MHC-I, MHC-II, CD86) Ubiquitinates and degrades death receptors (FAS, TRAIL-R1, TRAIL-R2) Ubiquitinates viral glycoproteins leading to lysosomal degradation Mediates 'Lys-63'-linked polyubiquitylation for vesicular trafficking and degradation