ArticleThe EMBO journal2005
Activation or suppression of NFkappaB by HPK1 determines sensitivity to activation-induced cell death.
Article in The EMBO journal, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 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
33 citing papers in PubMed, 78 citations in OpenAlex.
- From inhibition to degradation: advances in highly selective targeting strategies for HPK1.Molecular diversity · 2026Review
- HPK1 kinase inhibitor: a sufficient approach to target HPK1 to modulate T cell activation in cancer immunotherapy compared with degraders.Frontiers in immunology · 2025Article
- HPK1 citron homology domain regulates phosphorylation of SLP76 and modulates kinase domain interaction dynamics.Nature communications · 2024Article
- Mutant KRAS-activated circATXN7 fosters tumor immunoescape by sensitizing tumor-specific T cells to activation-induced cell death.Nature communications · 2024Article
- An updated review of small-molecule HPK1 kinase inhibitors (2016-present).Future medicinal chemistry · 2024Review
- Mutant KRAS Drives Immune Evasion by Sensitizing Cytotoxic T-Cells to Activation-Induced Cell Death in Colorectal Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Mitochondrial fission induces immunoescape in solid tumors through decreasing MHC-I surface expression.Nature communications · 2022Article
- Novel classes of immunotherapy for breast cancer.Breast cancer research and treatment · 2022Review
- The Kinase MAP4K1 Inhibits Cytosolic RNA-Induced Antiviral Signaling by Promoting Proteasomal Degradation of TBK1/IKKε.Microbiology spectrum · 2021Article
- Association of miR-499 Polymorphism and Its Regulatory Networks with Hashimoto Thyroiditis Susceptibility: A Population-Based Case-Control Study.International journal of molecular sciences · 2021Article
- Review
- The Crosstalk Between Hippo-YAP Pathway and Innate Immunity.Frontiers in immunology · 2020Review
- Transcriptional Analyses Identify Genes That Modulate Bovine Macrophage Response toFrontiers in cellular and infection microbiology · 2020Article
- NKILA lncRNA promotes tumor immune evasion by sensitizing T cells to activation-induced cell death.Nature immunology · 2018Article
- Exploiting Cell Death Pathways for Inducible Cell Elimination to Modulate Graft-versus-Host-Disease.Biomedicines · 2017Review
- Functional and biochemical characterization of a T cell-associated anti-apoptotic protein, GIMAP6.The Journal of biological chemistry · 2017Article
- Macroautophagy inhibition maintains fragmented mitochondria to foster T cell receptor-dependent apoptosis.The EMBO journal · 2016Article
- High-throughput RNAi screening of human kinases identifies predictors of clinical outcome in colorectal cancer patients treated with oxaliplatin.Oncotarget · 2015Article
- A new look at T cell receptor signaling to nuclear factor-κB.Trends in immunology · 2013Review
- Germinal center kinases in immune regulation.Cellular & molecular immunology · 2012Review
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 at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Restimulation of the T-cell receptor (TCR) in activated T cells induces CD95 (Fas/Apo-1)-mediated activation-induced cell death (AICD). The TCR-proximal mechanisms leading to AICD are elusive. Here we characterize hematopoietic progenitor kinase 1 (HPK1) as a differentially regulated TCR-proximal signaling protein involved in AICD of primary T cells. We show that HPK1 is a functional component of the endogenous IkappaB kinase (IKK) complex and is crucial for TCR-mediated NFkappaB activation. While full-length HPK1 enhances IKKbeta phosphorylation, siRNA-mediated knockdown of HPK1 blunts TCR-mediated NFkappaB activation and increases cell death. We also demonstrate proteolytic processing of HPK1 into HPK1-C, specifically in AICD-sensitive primary T cells. The cleavage product HPK1-C sequesters the inactive IKK complex and suppresses NFkappaB upon TCR restimulation by binding to IKKalpha and IKKbeta. T cells of HPK1-C transgenic mice are sensitized towards TCR-mediated AICD. Consequently, preventing HPK1-C generation in primary T cells by siRNA-mediated knockdown results in decreased AICD. Thus, these results show a novel mechanism of sensitization of T lymphocytes towards AICD by suppression of NFkappaB, and propose that HPK1 is a life/death switch in T lymphocytes.
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.