ArticleThe Journal of biological chemistry2011
Increased expression of the pro-apoptotic protein BIM, a mechanism for cAMP/protein kinase A (PKA)-induced apoptosis of immature T cells.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 34 citations in OpenAlex.
- The PDE4DIP-AKAP9 axis promotes lung cancer growth through modulation of PKA signalling.Communications biology · 2025Article
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- IL-33 and the PKA Pathway Regulate ILC2 Populations Expressing IL-9 and ST2.Frontiers in immunology · 2022Article
- Drug repurposing for targeting cyclic nucleotide transporters in acute leukemias - A missed opportunity.Seminars in cancer biology · 2021Review
- Complex roles of cAMP-PKA-CREB signaling in cancer.Experimental hematology & oncology · 2020Review
- Inactivation of oncogenic cAMP-specific phosphodiesterase 4D by miR-139-5p in response to p53 activation.eLife · 2016Article
- Article
- AMPK and PKA interaction in the regulation of survival of liver cancer cells subjected to glucose starvation.Oncotarget · 2016Article
- Mechanisms of cyclic AMP/protein kinase A- and glucocorticoid-mediated apoptosis using S49 lymphoma cells as a model system.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
- Regulation of Bim in Health and Disease.Oncotarget · 2015Review
- The natural compound forskolin synergizes with dexamethasone to induce cell death in myeloma cells via BIM.Scientific reports · 2015Article
- Prostaglandin E2 and programmed cell death 1 signaling coordinately impair CTL function and survival during chronic viral infection.Nature medicine · 2015Article
- Effect of cAMP signaling on expression of glucocorticoid receptor, Bim and Bad in glucocorticoid-sensitive and resistant leukemic and multiple myeloma cells.Frontiers in pharmacology · 2015Article
- miR-155 Controls Lymphoproliferation in LAT Mutant Mice by Restraining T-Cell Apoptosis via SHIP-1/mTOR and PAK1/FOXO3/BIM Pathways.PloS one · 2015Article
- Genomic and functional characterizations of phosphodiesterase subtype 4D in human cancers.Proceedings of the National Academy of Sciences of the United States of America · 2013Article
- Proteasomal degradation of Mcl-1 by maritoclax induces apoptosis and enhances the efficacy of ABT-737 in melanoma cells.PloS one · 2013Article
- The importance of the nurse cells and regulatory cells in the control of T lymphocyte responses.BioMed research international · 2013Review
- Article
- N-3 poly-unsaturated fatty acids shift estrogen signaling to inhibit human breast cancer cell growth.PloS one · 2012Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
The second messenger cAMP is proapoptotic for numerous cell types, but the mechanism for this proapoptotic action is not defined. Here, we use murine CD4(+)/CD8(+) S49 lymphoma cells and isolated thymocytes to assess this mechanism. In WT S49 cells, cAMP acts via protein kinase A (PKA) to induce G(1) phase cell cycle arrest and apoptosis. Treatment of WT and cAMP-Deathless (D-) S49 cells, which lack cAMP-promoted apoptosis, with the PKA agonist 8-(4-chlorophenylthio)-cAMP (CPT-cAMP) differentially regulates transcripts for numerous proapoptotic and antiapoptotic proteins. In contrast, kin-S49 cells (which lack PKA) show no cAMP-promoted changes in transcript expression. In this study, we use knockdown and overexpression approaches to define the role in cAMP/PKA-promoted apoptosis of the proapoptotic factor BIM (Bcl-2 interacting mediator of cell death), whose expression prominently increases in response to CPT-cAMP treatment of WT but not D- or kin- S49 cells. Conditional expression of BimL, one of the three major forms of Bim, increases apoptosis of WT, D-, and kin-S49 cells, whereas inhibition of cAMP-mediated induction of Bim isoforms by shRNAi attenuates CPT-cAMP-mediated apoptosis of WT S49 cells. Bim protein levels increase in subpopulations of CPT-cAMP-treated cells that undergo apoptosis. Thymic CD4(+)/CD8(+) cells isolated from Bim(-/-) mice corroborated the requirement of Bim expression for cAMP-promoted apoptosis. Thus, up-regulation of Bim appears to be an important determinant of cAMP/PKA-mediated apoptosis in immature T cells and may be a mechanism for such apoptosis in other cell types as well.
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