ArticleThe Journal of biological chemistry2010
Novel antileukemic compound ingenol 3-angelate inhibits T cell apoptosis by activating protein kinase Ctheta.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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.
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
7 citing papers in PubMed, 24 citations in OpenAlex.
- Ingenol-3-Angelate Enhances the B Cell Inhibitory Potential of Mesenchymal Stem Cells, Leading to Marked Alleviation of Lupus Symptoms in MRL.International journal of molecular sciences · 2024Article
- PKC agonism restricts innate immune suppression, promotes antigen cross-presentation and synergizes with agonistic CD40 antibody therapy to activate CD8Cancer letters · 2022Article
- Putative role of natural products as Protein Kinase C modulator in different disease conditions.Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences · 2021Review
- Discovery of Small Molecules for the Reversal of T Cell Exhaustion.Cell reports · 2019Article
- Article
- Protein kinase C (PKC) as a drug target in chronic lymphocytic leukemia.Medical oncology (Northwood, London, England) · 2013Review
- New developments in the treatment of actinic keratosis: focus on ingenol mebutate gel.Clinical, cosmetic and investigational dermatology · 2012Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
Members of the protein kinase C (PKC) family of serine-threonine kinases are important regulators of immune cell survival. Ingenol 3-angelate (PEP005) activates a broad range of PKC isoforms and induces apoptosis in acute myeloid leukemia cells by activating the PKC isoform PKCdelta. We show here that, in contrast to its effect on leukemic cells, PEP005 provides a strong survival signal to resting and activated human T cells. The antiapoptotic effect depends upon the activation of PKC. This PKC isoform is expressed in T cells but is absent in myeloid cells. Further studies of the mechanism involved in this process showed that PEP005 inhibited activated CD8(+) T cell apoptosis through the activation of NFkappaB downstream of PKC, leading to increased expression of the antiapoptotic proteins Mcl-1 and Bcl-x(L). Transfection of CD8(+) T cells with dominant-negative PKC diminished the prosurvival effect of PEP005 significantly. Ectopic expression of PKC in the acute myeloid leukemia cell line NB4 turned their response to PEP005 from an increased to decreased rate of apoptosis. Therefore, in contrast to myeloid leukemia cells, PEP005 provides a strong survival signal to T cells, and the expression of functional PKC influences whether PKC activation leads to an anti- or proapoptotic outcome in the cell types tested.
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.