ArticlePloS one2013
Non-secreted clusterin isoforms are translated in rare amounts from distinct human mRNA variants and do not affect Bax-mediated apoptosis or the NF-κB signaling pathway.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 32 papers.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
32 citing papers in PubMed, 48 citations in OpenAlex.
- Clusterin serum levels are elevated in patients with early rheumatoid arthritis and predict disease activity and treatment response.Scientific reports · 2021Trial
- Article
- The Emerging Role of the Molecular Chaperone Clusterin in Parkinson's Disease.International journal of molecular sciences · 2025Review
- Elucidating the function of clusterin in the progression of diabetic kidney disease.Frontiers in pharmacology · 2025Review
- Review
- Clusterin Expression in Colorectal Carcinomas.International journal of molecular sciences · 2023Review
- The Ins and Outs of Clusterin: Its Role in Cancer, Eye Diseases and Wound Healing.International journal of molecular sciences · 2023Review
- Clusterin and Its Isoforms in Oral Squamous Cell Carcinoma and Their Potential as Biomarkers: A Comprehensive Review.Biomedicines · 2023Review
- Clusterin/apolipoprotein J, its isoforms and Alzheimer's disease.Frontiers in aging neuroscience · 2023Article
- Glycosylated clusterin species facilitate Aβ toxicity in human neurons.Scientific reports · 2022Article
- Transcriptomes of Clusterin- and S100B-transfected neuronal cells elucidate protective mechanisms against hypoxia and oxidative stress in the hooded seal (Cystophora cristata) brain.BMC neuroscience · 2022Article
- Clusterin, other extracellular chaperones, and eye disease.Progress in retinal and eye research · 2022Review
- Novel insight into the role of clusterin on intraocular pressure regulation by modifying actin polymerization and extracellular matrix remodeling in the trabecular meshwork.Journal of cellular physiology · 2022Article
- RNA aptamers specific for transmembrane p24 trafficking protein 6 and Clusterin for the targeted delivery of imaging reagents and RNA therapeutics to human β cells.Nature communications · 2022Article
- HDL Accessory Proteins in Parkinson's Disease-Focusing on Clusterin (Apolipoprotein J) in Regard to Its Involvement in Pathology and Diagnostics-A Review.Antioxidants (Basel, Switzerland) · 2022Review
- The Influence of Clusterin Glycosylation Variability on Selected Pathophysiological Processes in the Human Body.Oxidative medicine and cellular longevity · 2022Review
- A pan-cancer analysis reveals role of clusterin (Frontiers in genetics · 2022Article
- Contribution of the Transcription Factors Sp1/Sp3 and AP-1 toInternational journal of molecular sciences · 2021Article
- Article
- Secreted Chaperones in Neurodegeneration.Frontiers in aging neuroscience · 2020Review
Corrections and comments
- Erratum issued
Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Clusterin, also known as apolipoprotein J, is expressed from a variety of tissues and implicated in pathological disorders such as neurodegenerative diseases, ischemia and cancer. In contrast to secretory clusterin (sCLU), which acts as an extracellular chaperone, the synthesis, subcellular localization and function(s) of intracellular CLU isoforms is currently a matter of intense discussion. By investigating human CLU mRNAs we here unravel mechanisms leading to the synthesis of distinct CLU protein isoforms and analyze their subcellular localization and their impact on apoptosis and on NF-κB-activity. Quantitative PCR-analyses revealed the expression of four different stress-inducible CLU mRNA variants in non-cancer and cancer cell lines. In all cell lines variant 1 represents the most abundant mRNA, whereas all other variants collectively account for no more than 0.34% of total CLU mRNA, even under stressed conditions. Overexpression of CLU cDNAs combined with in vitro mutagenesis revealed distinct translational start sites including a so far uncharacterized non-canonical CUG start codon. We show that all exon 2-containing mRNAs encode sCLU and at least three non-glycosylated intracellular isoforms, CLU1‑449, CLU21‑449 and CLU34‑449, which all reside in the cytosol of unstressed and stressed HEK‑293 cells. The latter is the only form expressed from an alternatively spliced mRNA variant lacking exon 2. Functional analysis revealed that none of these cytosolic CLU forms modulate caspase-mediated intrinsic apoptosis or significantly affects TNF-α-induced NF-κB-activity. Therefore our data challenge some of the current ideas regarding the physiological functions of CLU isoforms in pathologies.
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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.