E3 ubiquitin-protein ligase TRIM22 (TRIM22)

E3 ubiquitin-protein ligase TRIM22 is an interferon-induced member of the tripartite motif (TRIM) family of E3 ubiquitin ligases, characterized by a RING domain, B-box(es), a coiled-coil region, and a C-terminal B30.2/SPRY domain. TRIM22 localizes mainly in the nucleus and cytoplasm and can oligomerize to form higher-order complexes, including nuclear bodies. It is upregulated by Type I and II interferons and is also a direct p53 target gene. TRIM22 exerts broad antiviral effects by several mechanisms, including promoting proteasomal degradation of viral proteins, increasing heterochromatin and histone loading on viral genomes to repress their expression, and blocking viral assembly or release (notably for HIV-1, HBV, HSV-1, influenza, and others). In cancer biology, TRIM22 exhibits context-dependent roles, functioning as an antiproliferative agent in hematopoietic cells and as a pro-proliferative factor in some solid tumors like glioblastoma, where it can activate MAPK/ERK signaling by targeting Raf-1 for degradation. Variants and expression patterns of TRIM22 may influence individual susceptibility to various infections and possibly cancer progression. There are currently no direct TRIM22 inhibitors or drugs, but its pathway can be modulated by inhibitors of its downstream effectors.

Other names

Tripartite motif-containing 22RNF94STAF50GPSTAF5050 kDa-stimulated trans-acting factorRING finger protein 94RING-type E3 ubiquitin transferase TRIM22Staf-50Tripartite motif-containing protein 22stimulated trans-acting factor (50 kDa)tripartite binding motif 22tripartite motif protein TRIM22

Drugs targeting the downstream MAPK/ERK pathway (such as selumetinib) can mitigate TRIM22-driven signaling in cancer. General mechanisms for antiviral activity of TRIM22 involve its E3 ubiquitin ligase activity, promoting degradation of viral proteins or repressing viral gene transcription.