ArticleThe Journal of biological chemistry2012
CDK5 regulatory subunit-associated protein 1-like 1 (CDKAL1) is a tail-anchored protein in the endoplasmic reticulum (ER) of insulinoma cells.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 2 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
21 citing papers in PubMed, 2 syntheses or guidelines pooled it, 36 citations in OpenAlex.
- A HuGE Review and Meta-Analyses of Genetic Associations in New Onset Diabetes after Kidney Transplantation.PloS one · 2016Pooled it
- Genome-wide meta-analysis identifies five new susceptibility loci for cutaneous malignant melanoma.Nature genetics · 2015Pooled it
- CDKAL1-related single nucleotide polymorphisms are associated with insulin resistance in a cross-sectional cohort of Greek children.PloS one · 2014Trial
- Molecular Genetics of β-Cell Compensation in Gestational Diabetes Mellitus: Insights from CDKAL1, SLC30A8 and HHEX.International journal of molecular sciences · 2026Review
- Assessing individual genetic susceptibility to metabolic syndrome: interpretable machine learning method.Annals of medicine · 2025Article
- Involvement of Cdkal1 in the etiology of type 2 diabetes mellitus and microvascular diabetic complications: a review.Journal of diabetes and metabolic disorders · 2022Review
- Advances in CRISPR/Cas9.BioMed research international · 2022Review
- tRNA Biology in the Pathogenesis of Diabetes: Role of Genetic and Environmental Factors.International journal of molecular sciences · 2021Review
- Irp2 regulates insulin production through iron-mediated Cdkal1-catalyzed tRNA modification.Nature communications · 2020Article
- Silencing of the tRNA Modification Enzyme Cdkal1 Effects Functional Insulin Synthesis in NIT-1 Cells: tRNAFrontiers in molecular biosciences · 2020Article
- S-adenosylmethionine tRNA modification: unexpected/unsuspected implications of former/new players.International journal of biological sciences · 2020Review
- Human stem cell models: lessons for pancreatic development and disease.Genes & development · 2019Review
- Validation of Identified Susceptible Gene Variants for New-Onset Diabetes in Renal Transplant Recipients.Journal of clinical medicine · 2019Article
- An Isogenic Human ESC Platform for Functional Evaluation of Genome-wide-Association-Study-Identified Diabetes Genes and Drug Discovery.Cell stem cell · 2016Article
- Tail-anchored Protein Insertion in Mammals: FUNCTION AND RECIPROCAL INTERACTIONS OF THE TWO SUBUNITS OF THE TRC40 RECEPTOR.The Journal of biological chemistry · 2016Article
- Article
- Association of variants in CDKN2A/2B and CDKAL1 genes with gestational insulin sensitivity and disposition in pregnant Han Chinese women.Journal of diabetes investigation · 2015Article
- Transcriptomic Analysis of mRNAs in Human Monocytic Cells Expressing the HIV-1 Nef Protein and Their Exosomes.BioMed research international · 2015Article
- Joint identification of genetic variants for physical activity in Korean population.International journal of molecular sciences · 2014Article
- Different types of secondary information in the genetic code.RNA (New York, N.Y.) · 2014Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Genome-wide association studies have led to the identification of numerous susceptibility genes for type 2 diabetes. Among them is Cdkal1, which is associated with reduced β-cell function and insulin release. Recently, CDKAL1 has been shown to be a methylthiotransferase that modifies tRNA(Lys) to enhance translational fidelity of transcripts, including the one encoding proinsulin. Here, we report that out of several CDKAL1 isoforms deposited in public databases, only isoform 1, which migrates as a 61-kDa protein by SDS-PAGE, is expressed in human islets and pancreatic insulinoma INS-1 and MIN6 cells. We show that CDKAL1 is a novel member of the tail-anchored protein family and exploits the TCR40/Get3-assisted pathway for insertion of its C-terminal transmembrane domain into the endoplasmic reticulum. Using endo-β-N-acetylglucosaminidase H and peptide:N-glycosidase F sensitivity assays on CDKAL1 constructs carrying an N-glycosylation site within the luminal domain, we further established that CDKAL1 is an endoplasmic reticulum-resident protein. Moreover, we observed that silencing CDKAL1 in INS-1 cells reduces the expression of secretory granule proteins prochromogranin A and proICA512/ICA512-TMF, in addition to proinsulin and insulin. This correlated with reduced glucose-stimulated insulin secretion. Taken together, our findings provide new insight into the role of CDKAL1 in insulin-producing cells and help to understand its involvement in the pathogenesis of diabetes.
Indexed as
Identifiers
What OpenQuestion holds
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.