Zinc finger protein 598 (ZNF598)

Zinc finger protein 598 (ZNF598) is an E3 ubiquitin-protein ligase and zinc finger protein that plays a central role in ribosome-associated quality control (RQC), a fundamental cellular pathway active when ribosomes stall during translation. ZNF598 specifically recognizes collided ribosomes and, upon binding, ubiquitinates certain 40S ribosomal subunit proteins (notably RPS10 and RPS20), which signals for the recruitment of ribosome-splitting complexes leading to nascent peptide degradation and ribosome recycling. This protein is also important for the surveillance of prematurely polyadenylated mRNAs and translation repression via interactions with the 4EHP-GYF2 complex. ZNF598 is involved in RNA binding and contains both a RING domain characteristic of E3 ligases and C2H2-type zinc finger motifs typical for nucleic acid interaction. It has documented disease associations with frontotemporal dementia, amyotrophic lateral sclerosis, and neuromuscular disorders[1][2][3]. No approved drugs are known to target ZNF598 directly, but its key translational surveillance and stress response functions have implicated it as a pharmacological and research target.

Other names

E3 ubiquitin-protein ligase ZNF598FLJ00086HEL2ZNF598 {ECO:0000303|PubMed:28132843, ECO:0000312|HGNC:HGNC:28079}

Drugs or molecules targeting ZNF598 would be expected to modulate its E3 ubiquitin ligase activity, especially on ribosomal proteins during ribosome stalling, or alter its interaction with the 4EHP-GYF2 translation repression complex.