ArticleMolecular cancer research : MCR2012
The Proto-oncogene PKCι regulates the alternative splicing of Bcl-x pre-mRNA.
Article in Molecular cancer research : MCR, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 28 citations in OpenAlex.
- Ceramide Kinase Inhibition Drives Ferroptosis and Sensitivity to Cisplatin in Mutant KRAS Lung Cancer by Dysregulating VDAC-Mediated Mitochondria Function.Molecular cancer research : MCR · 2022Article
- Role of alternatively spliced, pro-survival Protein Kinase C delta VIII (PKCδVIII) in ovarian cancer.FASEB bioAdvances · 2022Article
- The three as: Alternative splicing, alternative polyadenylation and their impact on apoptosis in immune function.Immunological reviews · 2021Review
- Aberrant Bcl-x splicing in cancer: from molecular mechanism to therapeutic modulation.Journal of experimental & clinical cancer research : CR · 2021Review
- Protein Kinase C as a Therapeutic Target in Non-Small Cell Lung Cancer.International journal of molecular sciences · 2021Review
- The interaction of ceramide 1-phosphate with group IVA cytosolic phospholipase AScience signaling · 2019Article
- Modulation of the Apoptosis Gene Bcl-x Function Through Alternative Splicing.Frontiers in genetics · 2019Review
- hnRNP A1/A2 and Sam68 collaborate with SRSF10 to control the alternative splicing response to oxaliplatin-mediated DNA damage.Scientific reports · 2018Article
- Two novel atypical PKC inhibitors; ACPD and DNDA effectively mitigate cell proliferation and epithelial to mesenchymal transition of metastatic melanoma while inducing apoptosis.International journal of oncology · 2017Article
- Targeting oncogenic protein kinase Cι for treatment of mutant KRAS LADC.Small GTPases · 2017Article
- Pharmacology of Modulators of Alternative Splicing.Pharmacological reviews · 2017Review
- Melanoma Differentiation-associated Gene 7/IL-24 Exerts Cytotoxic Effects by Altering the Alternative Splicing of Bcl-x Pre-mRNA via the SRC/PKCδ Signaling Axis.The Journal of biological chemistry · 2016Article
- Caspase-9b Interacts Directly with cIAP1 to Drive Agonist-Independent Activation of NF-κB and Lung Tumorigenesis.Cancer research · 2016Article
- MLN4924 Synergistically Enhances Cisplatin-induced Cytotoxicity via JNK and Bcl-xL Pathways in Human Urothelial Carcinoma.Scientific reports · 2015Article
- Article
- Hallmarks of alternative splicing in cancer.Oncogene · 2014Review
- Atypical protein kinase Cι as a human oncogene and therapeutic target.Biochemical pharmacology · 2014Review
- Emerging mechanisms and consequences of calcium regulation of alternative splicing in neurons and endocrine cells.Cellular and molecular life sciences : CMLS · 2013Review
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
Two splice variants derived from the Bcl-x gene via alternative 5' splice site selection (5'SS) are proapoptotic Bcl-x(s) and antiapoptotic Bcl-x(L). Previously, our laboratory showed that apoptotic signaling pathways regulated the alternative 5'SS selection via protein phosphatase-1 and de novo ceramide. In this study, we examined the elusive prosurvival signaling pathways that regulate the 5'SS selection of Bcl-x pre-mRNA in cancer cells. Taking a broad-based approach by using a number of small-molecule inhibitors of various mitogenic/survival pathways, we found that only treatment of non-small cell lung cancer (NSCLC) cell lines with the phosphoinositide 3-kinase (PI3K) inhibitor LY294002 (50 μmol/L) or the pan-protein kinase C (PKC) inhibitor Gö6983 (25 μmol/L) decreased the Bcl-x(L)/(s) mRNA ratio. Pan-PKC inhibitors that did not target the atypical PKCs, PKCι and PKCζ, had no effect on the Bcl-x(L)/(s) mRNA ratio. Additional studies showed that downregulation of the proto-oncogene, PKCι, in contrast to PKCζ, also resulted in a decrease in the Bcl-x(L)/(s) mRNA ratio. Furthermore, downregulation of PKCι correlated with a dramatic decrease in the expression of SAP155, an RNA trans-acting factor that regulates the 5'SS selection of Bcl-x pre-mRNA. Inhibition of the PI3K or atypical PKC pathway induced a dramatic loss of SAP155 complex formation at ceramide-responsive RNA cis-element 1. Finally, forced expression of Bcl-x(L) "rescued" the loss of cell survival induced by PKCι siRNA. In summary, the PI3K/PKCι regulates the alternative splicing of Bcl-x pre-mRNA with implications in the cell survival of NSCLC cells.
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