Ask about this productRelated genes to: ZNF598 Blocking Peptide
- Gene:
- ZNF598 NIH gene
- Name:
- zinc finger protein 598
- Previous symbol:
- -
- Synonyms:
- FLJ00086, HEL2
- Chromosome:
- 16p13.3
- Locus Type:
- gene with protein product
- Date approved:
- 2004-03-01
- Date modifiied:
- 2017-12-01
Related products to: ZNF598 Blocking Peptide
Related articles to: ZNF598 Blocking Peptide
- 5-Azacytidine (5-AzaC) is a cytidine analog and is widely used to treat myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). Although its therapeutic activity is primarily attributed to hypomethylation resulting from DNA incorporation, the majority of 5-AzaC is incorporated into RNA. However, the functional consequences of 5-AzaC incorporation into RNA have been unknown. Here, we show that 5-AzaC treatment of cells leads to inhibition of protein synthesis. Ribo-seq, Disome-seq, and RNA-seq in cells treated with 5-AzaC exhibit a time-dependent C-to-G transversion signature in mRNAs within 2 h of treatment. These transversion events are enriched within footprint positions corresponding to the A-site of monosomes or leading stalled ribosome in a disome complex. Consistently, ribosome and disome footprints are accumulated at sites with C-rich codons in the A-site, specifically with the codons containing a C in the second position. 5-AzaC activates the integrated stress response (ISR) and the ribotoxic stress response (RSR) in a GCN2- and ZAK-dependent manner, consistent with disome-mediated signaling. Furthermore, loss of the Ribosome Quality Control (RQC) factor, ZNF598, sensitizes cells to 5-AzaC. Collectively, our results support a model where 5-AzaC is rapidly incorporated into mRNAs, disrupts decoding, and triggers disome-mediated signaling pathways, which contribute to its cytotoxicity. These findings suggest that translation disruption represents an additional layer of 5-AzaC's mechanism of action, alongside its known DNA-mediated effects. - Source: PubMed
Publication date: 2026/03/31
Roberson Alexis BMarks JamesPitts RubyTamilselvam BavavarshiniGrieb BrianTansey William PMeydan Sezen - Clearance of arrested nascent polypeptides resulting from ribosomal stalling is essential for proteostasis. Stalled endoplasmic reticulum (ER)-bound ribosomes are marked by ubiquitin-fold modifier 1 (UFM1) on the large ribosomal subunit protein RPL26, but the precise role of this modification in ribosome-associated quality control (RQC) remains poorly understood. Here, we define the interplay between the UFMylation machinery and the RQC in clearing arrested polypeptides upon ribosome stalling at the ER. Proteomic analysis shows that RQC factors associate with UFMylated ribosomes. Functional assays demonstrate that ribosome rescue factors ZNF598 and ASC-1 recognize and split stalled ribosomes at the ER, a prerequisite for RPL26 UFMylation. The UFM1 E3 ligase complex then binds and UFMylates the post-split 60S-peptidyl-tRNA complex, facilitating access of RQC factors. Depletion of the NEMF/LTN1 complex leads to accumulation of UFMylated ribosomes, whereas impaired UFMylation weakens NEMF/LTN1 binding to ER-stalled ribosomes, supporting a physical link between these pathways. These findings demonstrate that RQC cooperates with the UFMylation machinery to overcome the topological constraints of clearing the arrested polypeptides at the ER. - Source: PubMed
Publication date: 2026/03/25
Mihailovic MilicaAnisimova Aleksandra SErte BuZhan NiStyliara IoannaDagdas YasinKaragöz Gülsün Elif - Human immunodeficiency virus type 1 (HIV-1) remains a severe global public health threat. As a key transcription activator, the HIV-1 Tat protein is essential for viral replication and latency establishment or reactivation. Therefore, to discover the key factors regulating Tat stability and the underlying mechanisms is helpful to provide the essential target for HIV-1 control. Here, we identify the E3 ubiquitin ligase Zinc Finger Protein (ZNF598) as a positive regulator of Tat stability, which reduces the K48-linked ubiquitination and prevents the proteasomal degradation of Tat. The regulatory effect of ZNF598 on Tat abundance is independent of its E3 ligase activity. Importantly, ZNF598 promotes HIV-1 replication and latent reactivation in HIV-1 target cells. Furthermore, ZNF598 knockdown enhances the inhibitory effectiveness of Tat inhibitors against HIV-1. ZNF598 also exerts similar effects across multiple HIV-1 strains with different tropisms and Tat variants, suggesting that ZNF598 could serve as a broad-spectrum antiviral target. - Source: PubMed
Publication date: 2026/03/10
Shi HongyunHou YubaoWang HuihanHuan ChenWang YingchaoWang HongZhang Wenyan - Translation elongation defects activate the integrated stress response (ISR), but whether and how ribosome stalls are cleared to enable mRNA release for ribonucleoprotein (RNP) granule assembly remain unclear. We show that blocking tRNA aminoacylation generates persistent uncollided ribosome stalls that inhibit stress granule and P-body assembly despite robust ISR activation. Collided ribosomes are rapidly cleared by ZNF598-dependent ribosome-associated quality control within 4 h, while uncollided stalls resist clearance and persist for >16 h. Puromycin releases persistent stalls and restores RNP granule formation. The block in stress granule assembly is generalizable across tRNA synthetase inhibitors and amino acid deprivation. Therefore, stress granules represent signal integrators reporting translation elongation status when initiation is suppressed. Our findings reveal that translation quality control pathways selectively clear collided ribosomes, establish that translation elongation stress uncouples RNP granule assembly from the ISR, and suggest that tolerating uncollided stalls may be adaptive for cotranslational processes essential for cellular function. - Source: PubMed
Publication date: 2026/04/01
Baymiller MaxHelton Noah SDodd BenjaminMoon Stephanie L - (Macro)autophagy is a conserved cellular degradation pathway that delivers substrates to lysosomes via autophagosomes. Among various physiological stimuli, nutrient starvation is the most potent inducer of autophagy. In response to starvation, transcription factor EB (TFEB) is activated and up-regulates a broad set of autophagy-related genes. However, the mechanisms by which TFEB promotes autophagosome biogenesis remain incompletely understood. Here, we demonstrate that TFEB-mediated transcriptional induction of (SQSTM1; p62) triggers the formation of SQSTM1-positive bodies that recruit essential autophagy factors, thereby initiating autophagosome biogenesis. Genetic disruption of TFEB-dependent SQSTM1 regulation markedly impairs starvation-induced autophagy, underscoring the critical role of the TFEB-SQSTM1 axis in the autophagic response to nutrient stress. Furthermore, we show that these SQSTM1 bodies contain ubiquitinated ribosomal proteins and that TFEB promotes ribosomal protein ubiquitination by inducing the E3 ubiquitin ligase ZNF598. Collectively, our findings uncover a transcriptionally coordinated mechanism that regulates both autophagosome biogenesis and substrate ubiquitination, facilitating efficient cargo clearance during starvation-induced autophagy. - Source: PubMed
Publication date: 2026/01/01
Iavazzo MariaCinque LauraLevantovsky SophieMorrone CastreseMonfregola JleniaRaimondi AndreaPolishchuk ElenaDe Cegli RossellaCarrella DiegoNusco EdoardoFerrante LuigiSacco FrancescaFrankel Lisa BBehrends ChristianSettembre Carmine