Involvement of Protein Kinase C-β and Ceramide in Tumor Necrosis Factor-α-induced but Not Fas-induced Apoptosis of Human Myeloid Leukemia Cells

Laouar, Amale; Glesne, David; Huberman, Eliezer

doi:10.1074/jbc.274.33.23526

Cited by 46 publications

(38 citation statements)

References 71 publications

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“…As the agents which regulate activities of PKC, such as PMA or H-7, caused alteration of the levels of phosphorylated-Bcl10, Bcl10 could be directly phosphorylated by PKC. A variety of reports have suggested that PKC can act as a potentiator of apoptosis induced by stimuli such as TNF (Laouar et al, 1999;Takada et al, 1999). It is possible that Bcl10 might be a novel target molecule involved in the signaling of PKC-mediated apoptosis.…”

Section: Discussionmentioning

confidence: 99%

Interchangeable binding of Bcl10 to TRAF2 and cIAPs regulates apoptosis signaling

et al. 2001

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Bcl10 was identi®ed as a candidate gene responsible for low grade B cell lymphomas of mucosa-associated lymphoid tissue. Overexpression of Bcl10 in cultured cells was reported to promote apoptosis, however, the mechanism of regulation of apoptosis mediated by Bcl10 has not been demonstrated. In the present study, we analysed the apoptosis signaling pathway mediated by Bcl10, focusing on phosphorylation of Bcl10 and the dynamic interaction with its binding partners during apoptosis. Previously, we have demonstrated that Bcl10 potentially interacts with the other apoptosis regulator, TNF receptor associated factor-2 (TRAF2) and inhibitor of apoptosis proteins (cIAPs). The present results showed that the complex formation of these molecules was regulated by phosphorylation of Bcl10, that is, phosphorylation of Bcl10 resulted in binding of Bcl10 to cIAPs and the dissociation of it from TRAF2. Moreover, hyperphosphorylation of Bcl10 enhanced apoptosis, suggesting that changes in the binding partners of Bcl10 were correlated to the promotion of apoptosis as mediated by Bcl10. Indeed, the mutant which was deleted from the binding site of Bcl10 for cIAPs, could not induce apoptosis. These ®ndings indicate that Bcl10 is a mediator of apoptosis signaling, by switching over binding to cIAPs from TRAF2 through the events of Bcl10 phosphorylation. Oncogene (2001) 20, 4317 ± 4323.

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Section: Discussionmentioning

confidence: 99%

Interchangeable binding of Bcl10 to TRAF2 and cIAPs regulates apoptosis signaling

et al. 2001

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“…Numerous studies in myeloid cells have shown that PKC␤ functions in the apoptotic response to PMA (31)(32)(33)(34)(35). U937 or HL60 cells treated with PMA undergo apoptosis (31)(32)(33)(34)(35)(36). Cell lines deficient in PKC␤ are resistant to PMA-induced apoptosis, but the phenotype can be restored by ectopic expression of PKC␤ (31)(32)(33)(34)(35).…”

Section: Fig 2 Chromatin Immunoprecipitation Analysis Showing Intermentioning

confidence: 99%

“…U937 or HL60 cells treated with PMA undergo apoptosis (31)(32)(33)(34)(35)(36). Cell lines deficient in PKC␤ are resistant to PMA-induced apoptosis, but the phenotype can be restored by ectopic expression of PKC␤ (31)(32)(33)(34)(35). Events downstream of PKC␤ may include production of TNF␣, stimulation of ceramide synthesis, and activation of caspases (33,36).…”

Section: Fig 2 Chromatin Immunoprecipitation Analysis Showing Intermentioning

confidence: 99%

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A Chromatin Immunoprecipitation Screen Reveals Protein Kinase Cβ as a Direct RUNX1 Target Gene

Hug

Ahmed

Robbins

et al. 2004

Journal of Biological Chemistry

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RUNX1 (also known as AML1) is a DNA-binding transcription factor that functions as a tumor suppressor and developmental determinant in hematopoietic cells. Target promoters have been identified primarily through the use of differential expression strategies and candidate gene approaches but not biochemical screens. Using a chromatin immunoprecipitation screen, we identified protein kinase C␤ as a direct RUNX1 target gene and demonstrate that endogenous RUNX1 binds the chromatinized protein kinase C␤ promoter of U937 cells. A phylogenetically conserved RUNX1-binding site within the PKC␤ promoter binds RUNX1 in electrophoretic mobility shift analyses and confers RUNX1 responsiveness on a heterologous promoter. Changes in RUNX1 activity affect endogenous protein kinase C␤ expression, and a dominant-negative form of RUNX1 protects U937 cells from apoptotic stimuli previously shown to be dependent on protein kinase C␤. This protection can be reversed by the ectopic expression of protein kinase C␤. Together these findings demonstrate that protein kinase C␤ is a direct, downstream target of RUNX1 and links RUNX1 to a myeloid apoptotic pathway.

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“…31 ± 34 Likewise, PKCb appears to be required for ceramide and TNFa-induced apoptosis in HL-60 cells. 35 PKCd is cleaved and activated in a caspase dependent manner in response to a variety of apoptotic stimuli, and expression of activated PKCd has been shown to induce apoptosis in several cell types. 21,36 ± 38 Recent work from our laboratory demonstrates that inhibition of endogenous PKCd blocks etoposide induced apoptosis in salivary acinar cells.…”

Section: Introductionmentioning

confidence: 99%

Activation of PKC is sufficient to induce an apoptotic program in salivary gland acinar cells

et al. 2000

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Accumulating evidence suggests that specific isoforms of PKC may function to promote apoptosis. We show here that activation of the conventional and novel isoforms of PKC with 12-O-tetradecanoyl phorbol-13-ester (TPA) induces apoptosis in salivary acinar cells as indicated by DNA fragmentation and activation of caspase-3. TPA-induced DNA fragmentation, caspase-3 activation, and morphologic indicators of apoptosis, can be enhanced by pretreatment of cells with the calpain inhibitor, calpeptin, prior to the addition of TPA. Analysis of PKC isoform expression by immunoblot shows that TPAinduced downregulation of PKCa and PKCd is delayed in cells pre-treated with calpeptin, and that this correlates with an increase of these isoforms in the membrane fraction of cells. TPA-induced apoptosis is accompanied by biphasic activation of the c-jun-N-terminal kinase (JNK) pathway and inactivation of the extracellular regulated kinase (ERK) pathway. Expression of constitutively activated PKCa or PKCd, but not kinase negative mutants of these isoforms, or constitutively activated PKCe, induces apoptosis in salivary acinar cells, suggesting a role for these isoforms in TPAinduced apoptosis. These studies demonstrate that activation of PKC is sufficient for initiation of an apoptotic program in salivary acinar cells.

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Involvement of Protein Kinase C-β and Ceramide in Tumor Necrosis Factor-α-induced but Not Fas-induced Apoptosis of Human Myeloid Leukemia Cells

Cited by 46 publications

References 71 publications

Interchangeable binding of Bcl10 to TRAF2 and cIAPs regulates apoptosis signaling

Interchangeable binding of Bcl10 to TRAF2 and cIAPs regulates apoptosis signaling

A Chromatin Immunoprecipitation Screen Reveals Protein Kinase Cβ as a Direct RUNX1 Target Gene

Activation of PKC is sufficient to induce an apoptotic program in salivary gland acinar cells

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