ArticleCancer research2013
Cowden syndrome-related mutations in PTEN associate with enhanced proteasome activity.
Article in Cancer research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 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.
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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
17 citing papers in PubMed, 1 synthesis or guideline pooled it, 24 citations in OpenAlex.
- A Systematic Review of the Prevalence of Germline BRCA mutations in North Asia Breast Cancer Patients.Asian Pacific journal of cancer prevention : APJCP · 2024Pooled it
- Activin A Secreted by Cancer-Associated Fibroblasts Reduces the Sensitivity of Breast Cancer Cells to Ixazomib via Inhibition of Proteasome Activity.Biomolecules · 2025Article
- Construction destruction: Contribution of dyregulated proteostasis to neurodevelopmental disorders.Current opinion in neurobiology · 2025Review
- Article
- Domestic Animal Models of Central Nervous System Tumors: Focus on Meningiomas.Life (Basel, Switzerland) · 2023Review
- Nuclear PTEN's Functions in Suppressing Tumorigenesis: Implications for Rare Cancers.Biomolecules · 2023Review
- New germline mutations in non-BRCA genes among breast cancer women of Mongoloid origin.Molecular biology reports · 2020Article
- PTEN in Hereditary and Sporadic Cancer.Cold Spring Harbor perspectives in medicine · 2020Review
- Genomic stratification and liquid biopsy in a rare adrenocortical carcinoma (ACC) case, with dual lung metastases.Cold Spring Harbor molecular case studies · 2019Article
- Dynamics and structural stability effects of germline PTEN mutations associated with cancer versus autism phenotypes.Journal of biomolecular structure & dynamics · 2019Article
- PTEN-opathies: from biological insights to evidence-based precision medicine.The Journal of clinical investigation · 2019Review
- Early Onset Multiple Primary Tumors in Atypical Presentation of Cowden Syndrome Identified by Whole-Exome-Sequencing.Frontiers in genetics · 2018Article
- Drugging the addict: non-oncogene addiction as a target for cancer therapy.EMBO reports · 2016Review
- Controlling PTEN (Phosphatase and Tensin Homolog) Stability: A DOMINANT ROLE FOR LYSINE 66.The Journal of biological chemistry · 2016Article
- A Retroviral CRISPR-Cas9 System for Cellular Autism-Associated Phenotype Discovery in Developing Neurons.Scientific reports · 2016Article
- Balancing Proliferation and Connectivity in PTEN-associated Autism Spectrum Disorder.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2015Review
- Breast cancer in young women: special considerations in multidisciplinary care.Journal of multidisciplinary healthcare · 2014Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Germline mutations in PTEN have been described in a spectrum of syndromes that are collectively known as PTEN hamartoma tumor syndrome (PHTS). In addition to being mutated in the germline in PHTS, somatic loss-of-function PTEN mutations are seen in a wide range of sporadic human tumors. Here, we show evidence of upregulated proteasome activity in PHTS-derived lymphoblasts, Pten knock-in mice and cell lines expressing missense and nonsense PTEN mutations. Notably, elevated nuclear proteasome activity occurred in cells expressing the nuclear mislocalized PTEN-K62R mutant, whereas elevated cytosolic proteasome activity was observed in cells expressing the cytosolic-predominant mutant PTEN (M3M4 and C136R). Treatment with proteasome inhibitor MG-132 was able to restore both nonsense and missense mutant PTEN protein levels in vitro. PHTS patients with destabilizing PTEN mutations and proteasome hyperactivity are more susceptible to develop neurologic symptoms such as mental retardation and autism than mutation-positive patients with normal proteasome activity. A detailed molecular and functional analysis shows that PTEN mutants most likely cause proteasome hyperactivity via 2 different mechanisms, namely, induction of proteotoxic stress and loss of protein phosphatase activity. These results provide novel insights into the cellular functions of PTEN and reveal molecular mechanisms whereby PTEN mutations increase proteasome activity and lead to neurologic phenotypes.
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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.