E3 ubiquitin-protein ligase ZNF598

Definition:

E3 ubiquitin-protein ligase that plays a key role in the ribosome quality control (RQC), a pathway that takes place when a ribosome has stalled during translation. Required for ribosomes to terminally stall during translation of poly(A) sequences by mediating monoubiquitination of 40S ribosomal protein RPS10/eS10, RPS20/uS10 and RPS3/uS3. Stalling precludes synthesis of a long poly-lysine tail and initiates the RQC pathway to degrade the potentially detrimental aberrant nascent polypeptide. Also acts as a component of the 4EHP-GYF2 complex, a multiprotein complex that acts as a repressor of translation initiation.

References:

[1]. Masahiro Morita, et al. A novel 4EHP-GIGYF2 translational repressor complex is essential for mammalian development. Mol Cell Biol. 2012 Sep;32(17):3585-93. [Content Brief]

[2]. Szymon Juszkiewicz, et al. Initiation of Quality Control during Poly(A) Translation Requires Site-Specific Ribosome Ubiquitination. Mol Cell. 2017 Feb 16;65(4):743-750.e4. [Content Brief]

[3]. Elayanambi Sundaramoorthy, et al. ZNF598 and RACK1 Regulate Mammalian Ribosome-Associated Quality Control Function by Mediating Regulatory 40S Ribosomal Ubiquitylation. Mol Cell. 2017 Feb 16;65(4):751-760.e4. [Content Brief]

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