We have examined the regulation of the c-Jun NH2-terminal kinase (JNK) subfamily of mitogen-activated protein kinases (MAPKs) in response to inhibition of DNA replication during the cell cycle of human T-lymphocytes. In this study, we demonstrate that JNK is rapidly activated following release of T-lymphocytes from G1/S-phase arrest and that this activation precedes resumption of DNA synthesis upon S-phase progression. We also show that activation of JNK correlates with dissociation of the cyclin-dependent protein kinase (CDK) inhibitor, p21WAF1, from JNK1. Since JNK1 isolated from T-lymphocytes by immunoprecipitation can be inhibited by recombinant p21WAF1 in vitro, these data suggest that JNK activation may be regulated in part by its dissociation from p21WAF1. The observation of a dynamic, physical association of native JNK1 and p21WAF1 in vivo has not previously been described and suggests a novel mechanism for JNK-mediated regulation of the cell cycle of human T-lymphocytes.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1242/jcs.111.15.2247 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Syngeneic natural killer cell therapy activates dendritic and T cells in metastatic lungs and effectively treats low-burden metastases.
Elife
January 2025
Institute of Molecular Biology, Academia Sinica, Taipei, Taiwan.
Natural killer (NK) cells can control metastasis through cytotoxicity and IFN-γ production independently of T cells in experimental metastasis mouse models. The inverse correlation between NK activity and metastasis incidence supports a critical role for NK cells in human metastatic surveillance. However, autologous NK cell therapy has shown limited benefit in treating patients with metastatic solid tumors.
View Article and Find Full Text PDFExosomes: Key Messengers Mediating the Interaction Between Tumor Cells and CD8 T Cells in the Tumor Microenvironment.
Int J Nanomedicine
January 2025
Department of Thoracic Surgery, the First Hospital of China Medical University, Shenyang, 110002, People's Republic of China.
In recent years, with an increasingly profound comprehension of the tumor microenvironment, it has been discovered that the constituent cells within the immune microenvironment, such as macrophages, CD4T cells, and CD8T cells, interact with tumor cells in manners conducive to tumorigenesis and progression. Exosomes play a pivotal role as essential mediators for intercellular material exchange and signal transmission in this context. Tumor cell-derived exosomes carrying cargo such as PD-L1 and ncRNAs engage with CD8T cells to induce cytotoxic responses and facilitate immune evasion, thereby promoting tumor advancement.
View Article and Find Full Text PDFAdvances in CAR T cell therapy: antigen selection, modifications, and current trials for solid tumors.
Front Immunol
January 2025
Department of Medicine, Division of Hematology/Oncology, David Geffen School of Medicine at University of California, Los Angeles (UCLA), Los Angeles, CA, United States.
Chimeric antigen receptor (CAR) T cell therapy has revolutionized the treatment of hematologic malignancies, achieving remarkable clinical success with FDA-approved therapies targeting CD19 and BCMA. However, the extension of these successes to solid tumors remains limited due to several intrinsic challenges, including antigen heterogeneity and immunosuppressive tumor microenvironments. In this review, we provide a comprehensive overview of recent advances in CAR T cell therapy aimed at overcoming these obstacles.
View Article and Find Full Text PDFEffective cancer immunotherapy combining mRNA-encoded bispecific antibodies that induce polyclonal T cell engagement and PD-L1-dependent 4-1BB costimulation.
Front Immunol
January 2025
Department of Antibody Engineering, Leadartis SL, Tres Cantos, Madrid, Spain.
Background: Immune checkpoint inhibitors have revolutionized cancer therapy, but many patients fail to respond or develop resistance, often due to reduced T cell activity. Costimulation via 4-1BB has emerged as a promising approach to enhance the effector function of antigen-primed T cells. Bispecific T cell-engaging (TCE) antibodies are an effective way to provide tumor-specific T cell receptor-mediated signaling to tumor-infiltrating lymphocytes.
View Article and Find Full Text PDFExpanding the Scope of Microvascular Inflammation: Unveiling Its Presence Beyond Antibody-Mediated Rejection Into T-Cell Mediated Contexts.
Transpl Int
January 2025
Department of Pathology, Erasmus Medical Center Rotterdam, Rotterdam, Netherlands.
Microvascular inflammation (MVI) in kidney transplant biopsies is mainly associated with antibody-mediated rejection (AMR), sparking debate within the Banff Classification of Renal Allograft Pathology regarding its exclusivity. This study reviewed the literature on MVI in T cell-mediated rejection (TCMR) and analyzed MVI in our transplant population. We searched English publications in MEDLINE, Embase, Web of Science, Cochrane, and Google Scholar until June 2024, focusing on glomerulitis (g), peritubular capillaritis (ptc), or MVI in kidney transplant biopsies classified as TCMR.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!