Susceptibility to apoptosis is restored in human leukemia HCW-2 cells following induction and stabilization of the apoptotic effector Bak

Chatterjee, Devasis; Pantazis, Panayotis; Li, Gang; Bremner, Theodore A.; Hendrickson, Eric A.; Wyche, James H.

doi:10.1038/sj.onc.1203757

Cited by 5 publications

(3 citation statements)

References 64 publications

(50 reference statements)

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“…The presence of Bik, Bak, Bax, Bad, and Bid has also been reported in the monocytic lineage. Subcellular localization of these proteins, from the cytoplasm to mitochondrial membrane, seems to promote apoptosis (137,138). Mcl-1 expression decreases in cells treated with flavopiridol, resulting in an increase of cell death in myelomonocytic leukemia cells (141).…”

Section: Figure 2 Signal Pathways Involve In Monocytes and Macrophagmentioning

confidence: 99%

Regulation of monocytes and macrophages cell fate

González-Mejia

Doseff²

2009

Front Biosci

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Monocytes and macrophages are central cells of the innate immune system, responding to a diverse repertoire of pathogens. These cells originate from a common myeloid precursor in the bone marrow and while sharing responsibilities during innate immunity, differ greatly in their lifespan. Normally, blood monocytes live for just few days before undergoing apoptosis. Macrophages, in contrast, live up for months. Monocytes' lifespan can switch dramatically, from prolonged survival during inflammation to apoptosis as inflammation resolves. Interestingly, many of the mechanisms mediating survival during inflammation and cancer also operate in monocyte/macrophage differentiation. Differentiation and inflammatory stimuli determine monocyte/macrophage lifespan, by blocking the apoptotic pathway and activating a myriad of survival pathways. How these complicated networks of survival and apoptotic regulators are integrated remains yet to be fully elucidated. The present review summarizes the different monocytes' subpopulations and their function during pathogen recognition. We discuss the role of the caspases and the mechanisms that determine monocytes/macrophages fate highlighting their significance in the regulation of inflammatory diseases.

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Section: Figure 2 Signal Pathways Involve In Monocytes and Macrophagmentioning

confidence: 99%

Regulation of monocytes and macrophages cell fate

González-Mejia

Doseff²

2009

Front Biosci

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“…Studying mice lacking both Bax and Bak genes (bax Ϫ / Ϫ bak Ϫ / Ϫ ) showed overlapping roles of these proteins in the regulation of apoptosis (Lindsten et al, 2000). Like Bax, Bak has been shown to induce the loss of mitochondrial membrane potential and lead to cytochrome c release, whereas Bcl-2 and Bcl-X L prevent these events (Eskes et al, 1998;Shimizu et al, 1999;Chatterjee et al, 2000;Wei et al, 2000). However, Bax exists in the cytosol of healthy cells and translocates to the mitochondria during apoptosis, whereas Bak constitutively resides on mitochondrial membranes in healthy cells.…”

Section: Bak Colocalizes With Bax In the Apoptotic Clusters Whereas Bid And Bad Do Notmentioning

confidence: 99%

Bax and Bak Coalesce into Novel Mitochondria-Associated Clusters during Apoptosis

Nechushtan

Smith

Lamensdorf

et al. 2001

The Journal of Cell Biology

427

341

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Bax is a member of the Bcl-2 family of proteins known to regulate mitochondria-dependent programmed cell death. Early in apoptosis, Bax translocates from the cytosol to the mitochondrial membrane. We have identified by confocal and electron microscopy a novel step in the Bax proapoptotic mechanism immediately subsequent to mitochondrial translocation. Bax leaves the mitochondrial membranes and coalesces into large clusters containing thousands of Bax molecules that remain adjacent to mitochondria. Bak, a close homologue of Bax, colocalizes in these apoptotic clusters in contrast to other family members, Bid and Bad, which circumscribe the outer mitochondrial membrane throughout cell death progression. We found the formation of Bax and Bak apoptotic clusters to be caspase independent and inhibited completely and specifically by Bcl-XL, correlating cluster formation with cytotoxic activity. Our results reveal the importance of a novel structure formed by certain Bcl-2 family members during the process of cell death.

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“…Following death triggering, proapoptotic members of the Bcl-2 family are known to stimulate a cascade of downstream events, including processing of procaspases to their active forms (19). To investigate whether introduction of Fc⑀-Bak into target cells initiates one of the pathways finally leading to apoptosis, we examined the activation of caspase-3 by Western blot analysis of protein extracts from cells treated with h-Fc⑀ 2-4 -Bak and h-Fc⑀ 3 -Bak.…”

Section: Apoptotic Effect Of Chimeric Proteins On Various Cell Linesmentioning

confidence: 99%

Apoptosis-Inducing Human-Origin Fcε-Bak Chimeric Proteins for Targeted Elimination of Mast Cells and Basophils: A New Approach for Allergy Treatment

Belostotsky

Lorberboum-Galski

2001

The Journal of Immunology

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During the past few years, many chimeric proteins have been developed to specifically target and kill cells expressing specific surface molecules. Generally these molecules carry a bacterial or plant toxin to destroy the unwanted cells. The major obstacle regarding these molecules in their clinical application is the immunogenicity and nonspecific toxicity associated with bacterial or plant toxins. We lately reported a new approach for construction of chimeric proteins: we successfully replaced bacterial or plant toxins with human apoptosis-inducing proteins. The resulting chimeras were shown to specifically induce apoptosis in the target cells. Taking advantage of the human apoptosis inducing proteins Bak and Bax as novel killing components, we have now constructed new chimeric proteins targeted against the human FcεRI, expressed mainly on mast cells and basophils. These cells are the main effectors of the allergic response. Treatment of the target cells with the new chimeric proteins, termed Fcε-Bak/Bax, had a dramatic effect on cell survival, causing apoptosis. The effect was specific to cells expressing the FcεRI of both human and, very unexpectedly, also of mouse origin. Moreover, interaction of the chimeric proteins with the mast cells did not cause degranulation. Fcε-Bak/Bax are new chimeric proteins of human origin and, as such, are expected to be both less immunogenic and less toxic and, thus, may be specific and efficient reagents for the treatment of allergic diseases.

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Susceptibility to apoptosis is restored in human leukemia HCW-2 cells following induction and stabilization of the apoptotic effector Bak

Cited by 5 publications

References 64 publications

Regulation of monocytes and macrophages cell fate

Regulation of monocytes and macrophages cell fate

Bax and Bak Coalesce into Novel Mitochondria-Associated Clusters during Apoptosis

Apoptosis-Inducing Human-Origin Fcε-Bak Chimeric Proteins for Targeted Elimination of Mast Cells and Basophils: A New Approach for Allergy Treatment

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