ArticleProceedings of the National Academy of Sciences of the United States of America1999
The tumor-suppressor activity of PTEN is regulated by its carboxyl-terminal region.
Article in Proceedings of the National Academy of Sciences of the United States of America, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 150 papers.
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Who cites it
150 citing papers in PubMed, 313 citations in OpenAlex.
- NDRG1-PTEN association modulates PTEN C-terminal tail phosphorylation in insulin-resistant neurons.Molecular and cellular biochemistry · 2026Article
- G0 or no-G0: phosphatase control of quiescence and cell cycle entry.Biochemical Society transactions · 2026Review
- Article
- Biology of PEST-containing nuclear proteins as potential targets in ovarian cancer (Review).Oncology letters · 2026Review
- Clinical benefit of additional whole-exome sequencing over panel sequencing in an all-comer real-world molecular tumor board.ESMO open · 2025Article
- PTEN defects in cancer, from gene to protein molecular causes and therapeutic targets.Discover oncology · 2025Review
- Regulation of PEST-containing nuclear proteins in cancer cells: implications for cancer biology and therapy.Frontiers in oncology · 2025Review
- Distribution and potential involvement of PTEN in the innate immune response during viral infections in Cherry Valley ducks.Frontiers in immunology · 2025Article
- Comprehensive computational analysis of deleterious nsSNPs inMolecular biology research communications · 2025Article
- Interactions between key genes and pathways in prostate cancer progression and therapy resistance.Frontiers in oncology · 2025Review
- Carbon Nanotube-Mediated Delivery of PTEN Variants: In Vitro Antitumor Activity in Breast Cancer Cells.Molecules (Basel, Switzerland) · 2024Article
- PTEN: an emerging target in rheumatoid arthritis?Cell communication and signaling : CCS · 2024Review
- Article
- Epigenetic regulation in lung cancer.MedComm · 2023Review
- Synthetic lethal approaches to target cancers with loss of PTEN function.Genes & diseases · 2023Article
- Novel anti-PTEN C2 domain monoclonal antibodies to analyse the expression and function of PTEN isoform variants.PloS one · 2023Article
- Mechanism of activation and the rewired network: New drug design concepts.Medicinal research reviews · 2022Review
- Review
- Comprehensive characterization of somatic variants associated with intronic polyadenylation in human cancers.Nucleic acids research · 2021Article
- PTENα functions as an immune suppressor and promotes immune resistance in PTEN-mutant cancer.Nature communications · 2021Article
90 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
PTEN is a recently identified tumor suppressor inactivated in a variety of cancers such as glioblastoma and endometrial and prostate carcinoma. It contains an amino-terminal phosphatase domain and acts as a phosphatidylinositol 3,4,5-trisphosphate phosphatase antagonizing the activity of the phosphatidylinositol 3-OH kinase. PTEN also contains a carboxyl-terminal domain, and we addressed the role of this region that, analogous to the amino-terminal phosphatase domain, is the target of many mutations identified in tumors. Expression of carboxyl-terminal mutants in PTEN-deficient glioblastoma cells permitted the anchorage-independent growth of the cells that otherwise was suppressed by wild-type PTEN. The stability of these mutants in cells was reduced because of rapid degradation. Although the carboxyl-terminal region contains regulatory PEST sequences and a PDZ-binding motif, these specific elements were dispensable for the tumor-suppressor function. The study of carboxyl-terminal point mutations affecting the stability of PTEN revealed that these were located in strongly predicted beta-strands. Surprisingly, the phosphatase activity of these mutants was affected in correlation with the degree of disruption of these structural elements. We conclude that the carboxyl-terminal region is essential for regulating PTEN stability and enzymatic activity and that mutations in this region are responsible for the reversion of the tumor-suppressor phenotype. We also propose that the molecular conformational changes induced by these mutations constitute the mechanism for PTEN inactivation.
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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.