ZNF598 K63 polyubiquitinates RPS10 (eS10) and RPS20 (uS10) of the 40S ribosomal subunit

Stable Identifier
R-HSA-9948301
Type
Reaction [transition]
Species
Homo sapiens
Compartment
ReviewStatus
5/5
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ZNF598, a ubiquitin E3 ligase, transfers ubiquitin from UBE2D1, UBE2D2, or UBE2D3 to lysine-138 and lysine-139 of 40S ribosomal subunit RPS10 (eS10) and lysine-8 of 40S ribosomal subunit RPS20 (uS10) (Juszkiewicz and Hegde 2017, Sundaramoorthy et al. 2017, Garzia et al. 2017, Juszkiewicz et al. 2018, Narita et al. 2022, Miścicka et al. 2024, also inferred from yeast homologs in Matsuo et al. 2017, Ikeuchi et al. 2019). Ubiquitination of collided ribosomes appears to be more efficient than ubiquitination of single ribosomes, however, collision is not required for ubiquitination (Miścicka et al. 2024). ZNF598 produces linkages between lysine-63 (K63) and terminal carboxyl residues of ubiquitin monomers (Narita et al. 2022, Miścicka et al. 2024). The K63-linked polyubiquitin serves as a scaffold for binding other proteins, in this case the ASCC2 subunit of the RQT complex (ASCC2:ASCC3:TRIP4).
Literature References
PubMed ID Title Journal Year
28065601 Initiation of Quality Control during Poly(A) Translation Requires Site-Specific Ribosome Ubiquitination

Juszkiewicz, S, Hegde, RS

Mol Cell 2017
36302773 A distinct mammalian disome collision interface harbors K63-linked polyubiquitination of uS10 to trigger hRQT-mediated subunit dissociation

Narita, M, Denk, T, Matsuo, Y, Sugiyama, T, Kikuguchi, C, Ito, S, Sato, N, Suzuki, T, Hashimoto, S, Machová, I, Tesina, P, Beckmann, R, Inada, T

Nat Commun 2022
28132843 ZNF598 and RACK1 Regulate Mammalian Ribosome-Associated Quality Control Function by Mediating Regulatory 40S Ribosomal Ubiquitylation

Sundaramoorthy, E, Leonard, M, Mak, R, Liao, J, Fulzele, A, Bennett, EJ

Mol Cell 2017
30293783 ZNF598 Is a Quality Control Sensor of Collided Ribosomes

Juszkiewicz, S, Chandrasekaran, V, Lin, Z, Kraatz, S, Ramakrishnan, V, Hegde, RS

Mol Cell 2018
38366554 Ribosomal collision is not a prerequisite for ZNF598-mediated ribosome ubiquitination and disassembly of ribosomal complexes by ASCC

Miścicka, A, Bulakhov, AG, Kuroha, K, Zinoviev, A, Hellen, CUT, Pestova, TV

Nucleic Acids Res 2024
28685749 The E3 ubiquitin ligase and RNA-binding protein ZNF598 orchestrates ribosome quality control of premature polyadenylated mRNAs

Garzia, A, Jafarnejad, SM, Meyer, C, Chapat, C, Gogakos, T, Morozov, P, Amiri, M, Shapiro, M, Molina, H, Tuschl, T, Sonenberg, N

Nat Commun 2017
Participants
Participates
Catalyst Activity

ubiquitin-protein transferase activity of ZNF598:Ub:UBE2D1,2,3:80S Ribosome:mRNA:peptidyl-tRNA with nascent peptide [cytosol]

Orthologous Events
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