ArticleProceedings of the National Academy of Sciences of the United States of America2006
ALADINI482S causes selective failure of nuclear protein import and hypersensitivity to oxidative stress in triple A syndrome.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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
43 citing papers in PubMed.
- The Retina in Patients With Triple A Syndrome: A Window Into Neurodegeneration?Frontiers in endocrinology · 2021Trial
- Triple A syndrome with a new mutation pattern, first documented case in Austria: a case report with literature review.Orphanet journal of rare diseases · 2026Review
- A novel compound heterozygosity in AAAS gene in two Greek siblings: expanding the genotypic landscape of Allgrove syndrome.Neurogenetics · 2026Article
- Pathologies at the gateway: exploring the link between nucleoporins and inherited diseases.Cellular and molecular life sciences : CMLS · 2026Review
- Gonadal Function and Reproductive Health Challenges in Triple a Syndrome: A Narrative Review.Medicina (Kaunas, Lithuania) · 2025Review
- Double 'A' phenotypes with mineralocorticoid deficiency: A rare presentation of Allgrove syndrome.Clinical pediatric endocrinology : case reports and clinical investigations : official journal of the Japanese Society for Pediatric Endocrinology · 2025Article
- Insights into genetic and clinical profiles of triple A syndrome in Sudanese children.Frontiers in endocrinology · 2025Article
- Nuclear pore and nucleocytoplasmic transport impairment in oxidative stress-induced neurodegeneration: relevance to molecular mechanisms in Pathogenesis of Parkinson's and other related neurodegenerative diseases.Molecular neurodegeneration · 2024Review
- Very early and severe presentation of Triple A syndrome - case report and review of the literature.Frontiers in endocrinology · 2024Review
- Generation of glucocorticoid-producing cells derived from human pluripotent stem cells.Cell reports methods · 2023Article
- SCARB1 downregulation in adrenal insufficiency with Allgrove syndrome.Orphanet journal of rare diseases · 2023Article
- Nuclear Pore Dysfunction in Neurodegeneration.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2022Review
- Cryo-EM structure of the inner ring from the Xenopus laevis nuclear pore complex.Cell research · 2022Article
- Sporadic Triple A (Allgrove) Syndrome with Novel Tandem Mutations.Internal medicine (Tokyo, Japan) · 2021Article
- Bilateral Recurrent Laryngeal Nerve Palsy following Total Thyroidectomy in Triple A Syndrome, an Unexpected but Critical Complication.Case reports in otolaryngology · 2021Article
- WD40-Repeat Proteins in Ciliopathies and Congenital Disorders of Endocrine System.Endocrinology and metabolism (Seoul, Korea) · 2020Review
- Nucleo-cytoplasmic transport defects and protein aggregates in neurodegeneration.Translational neurodegeneration · 2020Review
- Two novel truncating variants of the AAAS gene causative of the triple A syndrome.Journal of endocrinological investigation · 2020Article
- Neurological Phenotypes Associated with AAAS-Related Disorders: Spastic Ataxia and Complex Spastic Paraplegia.Cerebellum (London, England) · 2020Article
- A broad range of symptoms in allgrove syndrome: single center experience in Southeast Anatolia.Journal of endocrinological investigation · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Triple A syndrome is an autosomal recessive neuroendocrinological disease caused by mutations in a gene that encodes 546 amino acid residues. The encoded protein is the nucleoporin ALADIN, a component of nuclear pore complex (NPC). We identified a mutant ALADIN(I482S) that fails to target NPC and investigated the consequences of mistargeting using cultured fibroblasts (I482Sf) from a patient with triple A syndrome. ALADIN(I482S) affected a karyopherin-alpha/beta-mediated import pathway and decreased nuclear accumulations of aprataxin (APTX), a repair protein for DNA single-strand breaks (SSBs), and of DNA ligase I in I482Sf. This decrease was restored by wild-type ALADIN. ALADIN(I482S) had no effect on imports of M9/kap-beta2, BIB/kap-beta3, histone H1/importin 7, the ubiquitin conjugating enzyme UbcM2/importin 11, or the spliceosome protein U1A, indicating that ALADIN(I482S) selectively impaired transport of discrete import complexes through NPC. Cell survival assay showed hypersensitivity of I482Sf to l-buthionine-(S,R)-sulfoximine (BSO), a glutathione-depleting agent. BSO decreased nuclear APTX and ligase I levels in I482Sf and normal control fibroblasts, but increased SSBs only in I482Sf. These observations implied that I482Sf are hypersensitive to BSO and no longer sufficiently repair SSBs. Consistent with this notion, I482Sf transfected with both APTX and ligase I had increased resistance to BSO, whereas I482Sf transfected with LacZ vector remained hypersensitive to BSO. We propose that oxidative stress aggravates nuclear import failure, which is already compromised in patient cells. Consequent DNA damage, beyond the limited capacity of DNA repair proteins, i.e., APTX and ligase I, may participate in triggering cell death.
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.