ArticleProceedings of the National Academy of Sciences of the United States of America2000
Tcl1 enhances Akt kinase activity and mediates its nuclear translocation.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 140 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
140 citing papers in PubMed, 1 synthesis or guideline pooled it, 104 citations in OpenAlex.
- Validation of human telomere length multi-ancestry meta-analysis association signals identifies POP5 and KBTBD6 as human telomere length regulation genes.Nature communications · 2024Pooled it
- TCL1A mediates DNA methylation defects in recurrent hydatidiform mole with NLRP7 pathogenic variants.Nature communications · 2026Article
- New drug targets for acute myeloid leukemia identified through a comprehensive analysis of the plasma protein.BMC cancer · 2025Article
- Insights into PI3K/AKT signaling in B cell development and chronic lymphocytic leukemia.FEBS letters · 2025Review
- Exosomal mRNA Cargo are biomarkers of tumor and immune cell populations in pediatric osteosarcoma.Translational oncology · 2024Article
- CRISPR loss of function screening to identify genes involved in human primordial germ cell-like cell development.PLoS genetics · 2023Article
- Functional role of MicroRNA/PI3K/AKT axis in osteosarcoma.Frontiers in oncology · 2023Review
- TCL1A+ B cells predict prognosis in triple-negative breast cancer through integrative analysis of single-cell and bulk transcriptomic data.Open life sciences · 2023Article
- AktAR and Akt-STOPS: Genetically Encodable Molecular Tools to Visualize and Perturb Akt Kinase Activity at Different Subcellular Locations in Living Cells.Current protocols · 2022Article
- miRNAs in Lymphocytic Leukaemias-The miRror of Drug Resistance.International journal of molecular sciences · 2022Review
- EGFR signaling promotes nuclear translocation of plasma membrane protein TSPAN8 to enhance tumor progression via STAT3-mediated transcription.Cell research · 2022Article
- A role for AKT1 in nonsense-mediated mRNA decay.Nucleic acids research · 2021Article
- Review
- Identification of potential core genes in gastric cancer using bioinformatics analysis.Journal of gastrointestinal oncology · 2021Article
- Review
- Constitutive activation of Lyn kinase enhances BCR responsiveness, but not the development of CLL in Eµ-TCL1 mice.Blood advances · 2020Article
- Article
- Impact of Genetics on Mature Lymphoid Leukemias and Lymphomas.Cold Spring Harbor perspectives in medicine · 2020Review
- Control of Akt activity and substrate phosphorylation in cells.IUBMB life · 2020Review
- Metalearning approach for leukemia informative genes prioritization.Journal of integrative bioinformatics · 2020Article
80 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
The TCL1 oncogene at 14q32.1 is involved in the development of human mature T-cell leukemia. The mechanism of action of Tcl1 is unknown. Because the virus containing the v-akt oncogene causes T-cell lymphoma in mice and Akt is a key player in transduction of antiapoptotic and proliferative signals in T-cells, we investigated whether Akt and Tcl1 function in the same pathway. Coimmunoprecipitation experiments showed that endogenous Akt1 and Tcl1 physically interact in the T-cell leukemia cell line SupT11; both proteins also interact when cotransfected into 293 cells. Using several AKT1 constructs in cotransfection experiments, we determined that this interaction occurs through the pleckstrin homology domain of the Akt1 protein. We further demonstrated that, in 293 cells transfected with TCL1, the endogenous Akt1 bound to Tcl1 is 5-10 times more active compared with Akt1 not bound to Tcl1. The intracellular localization of Tcl1 and Akt1 in mouse fibroblasts was investigated by immunofluorescence. When transfected alone, Akt1 was found only in cytoplasm whereas Tcl1 was localized in the cytoplasm and in the nucleus. Interestingly, Akt1 was also found in the nucleus when AKT1 was cotransfected with TCL1, suggesting that Tcl1 promotes the transport of Akt1 to the nucleus. These findings were supported by the intracellular localization of Akt1 or Tcl1 when Tcl1 or Akt1, respectively, were confined to the specific cellular compartments. Thus, we demonstrate that Tcl1 is a cofactor of Akt1 that enhances Akt1 kinase activity and promotes its nuclear transport.
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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.