ArticleGenes & development2011
Uncoupling of GTP hydrolysis from eIF6 release on the ribosome causes Shwachman-Diamond syndrome.
Article in Genes & development, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04275479 (Endocrine Diabetes Screening in Patients With Shwachman-Diamond Syndrome DIABETES/ ENDOCRINE SURVEILLANCE IN SDS), which is not on this map. Cited by 170 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Endocrine Diabetes Screening in Patients With Shwachman-Diamond Syndrome DIABETES/ ENDOCRINE SURVEILLANCE IN SDS
Who cites it
170 citing papers in PubMed, 1 synthesis or guideline pooled it, 283 citations in OpenAlex.
- A Case Report of Shwachman-Diamond Syndrome Caused by Heterozygous Variants in the EFL1 Gene and Literature Review.Molecular genetics & genomic medicine · 2026Pooled it
- Ribosome biogenesis and selective translational control as oncogenic vulnerabilities in hematologic malignancies.Molecular cancer · 2026Review
- SNOR promotes translation restart after dormancy.Nature · 2026Article
- Homozygous Pathogenic Variant in Elongation Factor-Like 1 (EFL1) as a Causal Factor in Shwachman-Diamond Syndrome 2 in a Palestinian Child, With Distinct Ocular Manifestations.Molecular genetics & genomic medicine · 2026Article
- Functional impact of the eIF6 N106S mutation on ribosome biogenesis in wild type and Shwachman-Diamond syndrome cells.Molecular medicine (Cambridge, Mass.) · 2026Article
- Hydroxyl radical footprinting modification reveals an intradomain communication pathway in EFL1 disrupted by a Shwachman-Diamond syndrome-associated mutation.Protein science : a publication of the Protein Society · 2026Article
- A Novel Eukaryotic Ribosome Factor Enables Translation Restart Following Cellular Dormancy.bioRxiv : the preprint server for biology · 2026Article
- Eukaryote initiation factor 6 modulates small-cell lung carcinoma plasticity via the integrin-FAK signaling axis.Nature communications · 2026Article
- Proteome-wide C-degron activity profiling connects conditional regulation of the CTLH E3 ligase complex to ribosome biogenesis.bioRxiv : the preprint server for biology · 2026Article
- Review
- Emerging roles of ribosome translation in stem cells and stem cell therapy - a review.Cell & bioscience · 2025Review
- Reduced EIF6 dosage attenuates TP53 activation in models of Shwachman-Diamond syndrome.The Journal of clinical investigation · 2025Article
- Sequestration of ribosomal subunits as inactive 80S by targeting eIF6 limits mitotic exit and cancer progression.Nucleic acids research · 2025Article
- The assembly factor Reh1 is released from the ribosome during its initial round of translation.Nature communications · 2025Article
- SNORD113-114 cluster maintains haematopoietic stem cell self-renewal via orchestrating the translation machinery.Nature cell biology · 2025Article
- Case Report: A case report and literature review of shwachman-diamond syndrome concurrent with klinefelter syndrome.Frontiers in pediatrics · 2025Article
- Article
- Protein Multiple Conformation Prediction Using Multi-Objective Evolution Algorithm.Interdisciplinary sciences, computational life sciences · 2024Article
- Lethal Complications and Complex Genotypes in Shwachman Diamond Syndrome: Report of a Family with Recurrent Neonatal Deaths and a Case-Based Brief Review of the Literature.Children (Basel, Switzerland) · 2024Review
- Shwachman-Diamond syndrome mimicking mitochondrial hepatopathy.JPGN reports · 2024Article
110 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
17 authors at 9 institutions in 4 countries.
Funding
Abstract
Removal of the assembly factor eukaryotic initiation factor 6 (eIF6) is critical for late cytoplasmic maturation of 60S ribosomal subunits. In mammalian cells, the current model posits that eIF6 release is triggered following phosphorylation of Ser 235 by activated protein kinase C. In contrast, genetic studies in yeast indicate a requirement for the ortholog of the SBDS (Shwachman-Bodian-Diamond syndrome) gene that is mutated in the inherited leukemia predisposition disorder Shwachman-Diamond syndrome (SDS). Here, by isolating late cytoplasmic 60S ribosomal subunits from Sbds-deleted mice, we show that SBDS and the GTPase elongation factor-like 1 (EFL1) directly catalyze eIF6 removal in mammalian cells by a mechanism that requires GTP binding and hydrolysis by EFL1 but not phosphorylation of eIF6 Ser 235. Functional analysis of disease-associated missense variants reveals that the essential role of SBDS is to tightly couple GTP hydrolysis by EFL1 on the ribosome to eIF6 release. Furthermore, complementary NMR spectroscopic studies suggest unanticipated mechanistic parallels between this late step in 60S maturation and aspects of bacterial ribosome disassembly. Our findings establish a direct role for SBDS and EFL1 in catalyzing the translational activation of ribosomes in all eukaryotes, and define SDS as a ribosomopathy caused by uncoupling GTP hydrolysis from eIF6 release.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.