CD437, a synthetic retinoid, induces apoptosis in human respiratory epithelial cells via caspase-independent mitochondrial and caspase-8-dependent pathways both up-regulated by JNK signaling pathway

Boisvieux‐Ulrich, Emmanuelle; Sourdeval, Matthieu; Marano, Francelyne

doi:10.1016/j.yexcr.2005.02.005

Cited by 27 publications

(24 citation statements)

References 66 publications

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“…4), thus suggesting that the pro-apoptotic effect of TULA is specific for certain types of cell death. It is also possible that AIF functionally cooperates with caspases in the cell death cascades, being responsible for the early stages of apoptosis (34,39). In particular, a recent report indicates that large scale DNA degradation, which was thought to be a hallmark of the apoptotic effect of AIF, may be caspase-dependent, but agrees with the previous studies that AIF-dependent chromatin condensation is independent of caspases and represents an early step of the cell death, which precedes its caspase-dependent steps (45).…”

Section: Discussionmentioning

confidence: 99%

T-cell Ubiquitin Ligand Affects Cell Death through a Functional Interaction with Apoptosis-inducing Factor, a Key Factor of Caspase-independent Apoptosis

Collingwood

Smirnova

Bogush

et al. 2007

Journal of Biological Chemistry

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The lymphoid protein T-cell ubiquitin ligand (TULA)/suppressor of T-cell receptor signaling (Sts)-2 is associated with c-Cbl and ubiquitylated proteins and has been implicated in the regulation of signaling mediated by protein-tyrosine kinases. The results presented in this report indicate that TULA facilitates T-cell apoptosis independent of either T-cell receptor/ CD3-mediated signaling or caspase activity. Mass spectrometry-based analysis of protein-protein interactions of TULA demonstrates that TULA binds to the apoptosis-inducing protein AIF, which has previously been shown to function as a key factor of caspase-independent apoptosis. Using RNA interference, we demonstrate that AIF is essential for the apoptotic effect of TULA. Analysis of the subcellular localization of TULA and AIF together with the functional analysis of TULA mutants is consistent with the idea that TULA enhances the apoptotic effect of AIF by facilitating the interactions of AIF with its apoptotic co-factors, which remain to be identified. Overall, our results shed new light on the biological functions of TULA, a recently discovered protein, describing its role as one of very few known functional interactors of AIF.We recently identified TULA among multiple proteins that co-purified with c-Cbl from T-lymphoblastoid cells (1). TULA contains an N-terminal UBA domain, a centrally positioned SH3 2 domain, and a region of homology to phosphoglyceromutases, which was initially termed HCD ( Fig. 1) (1, 2). TULA binds to c-Cbl through its SH3 domain and to ubiquitin and ubiquitylated proteins through its UBA domain (1, 3). Dimerization of TULA through its phosphoglyceromutase domain has also been shown (3). Analysis of cell and tissue expression of TULA demonstrates that this protein is expressed primarily in T and B lymphocytes and is localized both in the cytoplasm and nucleus (1, 4). A mouse orthologue of TULA (Sts-2) was recently identified (4), as was a second member of the family, Sts-1 (5). Unlike TULA, Sts-1 is expressed ubiquitously (4, 5). (In this report we will use the term TULA for consistency.)TULA has been implicated in the regulation of cell signaling mediated by protein-tyrosine kinases. On the one hand, TULA was reported to increase activity of receptor protein-tyrosine kinases by inhibiting c-Cbl-driven down-regulation of their activated forms. This appears to be mediated by preventing interactions between ubiquitylated forms of activated proteintyrosine kinases and proteins recruiting them to the degradation pathway and, possibly, by decreasing the level of c-Cbl (1, 3). On the other, the lack of both proteins of the TULA/Sts family resulted in hyper-reactivity of T lymphocytes correlated with an increase in the activity of Zap-70, the molecular basis of which remained unclear (4). These results implied that the effect of TULA on protein-tyrosine kinases might not be the only mechanism through which TULA exerts its biological effect. Indeed, the presence in TULA of multiple functional domains and extensive stretches of amino...

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Section: Discussionmentioning

confidence: 99%

T-cell Ubiquitin Ligand Affects Cell Death through a Functional Interaction with Apoptosis-inducing Factor, a Key Factor of Caspase-independent Apoptosis

Collingwood

Smirnova

Bogush

et al. 2007

Journal of Biological Chemistry

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“…The role of caspases in the anoikis process was studied by using specific inhibitors, previously used in our model [27,42]. We first sought the caspase-dependence of mustardinduced cell detachment.…”

Section: Discussionmentioning

confidence: 99%

“…Cells were grown in DMEM/Ham F12 medium, 2% Ultroser G, 1% glutamine, 0.5% fungizone and antibiotics (100 U/mL penicillin, 100 µg/mL streptomycin) (Invitrogen, France), seeded at 30 000 cells/cm 2 in 6-or 12-well plates coated with type I collagen [3,4,27]. HeLa cells stably transfected with empty vector (pcDNA3, neo) or with human bcl-2 gene (provided by Dr. V. Goldmacher, USA) and HCT116 colon carcinoma (proficient, Bax −/− or Bak −/− ; provided by B.…”

Section: Cell Culturementioning

confidence: 99%

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Inhibition of caspase-dependent mitochondrial permeability transition protects airway epithelial cells against mustard-induced apoptosis

et al. 2006

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In the present study, the toxicity of yperite, SM, and its structural analogue mechlorethamine, HN2, was investigated in a human bronchial epithelial cell line 16HBE. Cell detachment was initiated by caspase-2 activation, down-regulation of Bcl-2 and loss of mitochondrial membrane potential. Only in detached cells, mustards induced apoptosis associated with increase in p53 expression, Bax activation, decrease in Bcl-2 expression, opening of the mitochondrial permeability transition pore, release of cytochrome c, caspase-2, -3, -8, -9 and -13 activation and DNA fragmentation. Apoptosis, occurring only in detached cells, could be recognized as anoikis and the mitochondrion, involved both in cell detachment and subsequent cell death, appears to be a crucial checkpoint. Based on our understanding of the apoptotic pathway triggered by mustards, we demonstrated that inhibition of the mitochondrial pathway by ebselen, melatonin and cyclosporine A markedly prevented mustard-induced anoikis, pointing to these drugs as interesting candidates for the treatment of mustard-induced airway epithelial lesions.

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“…They are known to activate JNK (Zhang et al, , 2003Wan et al, 2001;Garattini et al, 2004;Boisvieux-Ulrich et al, 2005), which is required for maximal apoptosis induction and precedes mitochondrial depolarization. Induction of apoptosis of breast and prostate cancer cells by AHPN is also associated with its inhibition of Akt activity (Farhana et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

Regulation of Nur77 nuclear export by c-Jun N-terminal kinase and Akt

et al. 2006

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Proapoptotic nuclear receptor family member Nur77 translocates from the nucleus to the mitochondria, where it interacts with Bcl-2 to trigger apoptosis. Nur77 translocation is induced by certain apoptotic stimuli, including the synthetic retinoid-related 6-[3-(1-adamantyl)-4-hydroxyphenyl]-2-naphthalenecarboxylic acid (AHPN)/ CD437 class. In this study, we investigated the molecular mechanism by which AHPN/CD437 analog (E)-4-[3-(1-adamantyl)-4-hydroxyphenyl]-3-chlorocinnamic acid (3-Cl-AHPC) induces Nur77 nuclear export. Our results demonstrate that 3-Cl-AHPC effectively activated Jun N-terminal kinase (JNK), which phosphorylates Nur77. Inhibition of JNK activation by a JNK inhibitor suppressed 3-Cl-AHPC-induced Nur77 nuclear export and apoptosis. In addition, several JNK upstream activators, including the phorbol ester TPA, anisomycin and MAPK kinase kinase-1 (MEKK1), phosphorylated Nur77 and induced its nuclear export. However, Nur77 phosphorylation by JNK, although essential, was not sufficient for inducing Nur77 nuclear export. Induction of Nur77 nuclear export by MEKK1 required a prolonged MEKK1 activation and was attenuated by Akt activation. Expression of constitutively active Akt prevented MEKK1-induced Nur77 nuclear export. Conversely, transfection of dominant-negative Akt or treatment with a phosphatidylinositol 3-kinase (PI3-K) inhibitor accelerated MEKK1-induced Nur77 nuclear export. Furthermore, mutation of an Akt phosphorylation residue Ser351 in Nur77 abolished the effect of Akt or the PI3-K inhibitor. Together, our results demonstrate that both activation of JNK and inhibition of Akt play a role in translocation of Nur77 from the nucleus to the cytoplasm.

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CD437, a synthetic retinoid, induces apoptosis in human respiratory epithelial cells via caspase-independent mitochondrial and caspase-8-dependent pathways both up-regulated by JNK signaling pathway

Cited by 27 publications

References 66 publications

T-cell Ubiquitin Ligand Affects Cell Death through a Functional Interaction with Apoptosis-inducing Factor, a Key Factor of Caspase-independent Apoptosis

T-cell Ubiquitin Ligand Affects Cell Death through a Functional Interaction with Apoptosis-inducing Factor, a Key Factor of Caspase-independent Apoptosis

Inhibition of caspase-dependent mitochondrial permeability transition protects airway epithelial cells against mustard-induced apoptosis

Regulation of Nur77 nuclear export by c-Jun N-terminal kinase and Akt

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