Macrophage Apoptosis by Anthrax Lethal Factor Through p38 MAP Kinase Inhibition

Park, Jin Mo; Greten, Florian R.; Li, Zhiwei; Karin, Michael

doi:10.1126/science.1073163

Cited by 470 publications

(478 citation statements)

References 28 publications

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“…Two principal B. anthracis toxin components, lethal factor (LF, a Zn 2+ -protease) and edema factor (EF, a calmodulin-and Ca 2+ -dependent adenylate cyclase) are enzymes transported into cells by a third polypeptide, PA; combinations of PA with LF and EF yield B. anthracis lethal toxin (LT) and B. anthracis edema toxin (ET), respectively, that function as bacterial virulence factors in producing many of the symptoms of anthrax [13][14][15][16][17][18]. The pivotal role played by PA in toxin cell entry forms the basis for the current licensed anthrax vaccine, AVA (Biothrax TM ), a sterile culture filtrate of avirulent, non-encapsulated, B. anthracis (stimulated to produce relatively large amounts of PA) mixed with formalin and benzethonium chloride, and combined with aluminum hydroxide [19].…”

Section: Discussionmentioning

confidence: 99%

“…Samples were retrieved from −70 • C storage that met preestablished criteria: (a) Vaccinations must have occurred within defined time intervals after receipt of the initial AVA injection (day 0 [dose #1], day 14 [range [11][12][13][14][15][16][17][18][19][20][21] ). (b) Pre-injection sera were defined as those taken on the day of each vaccine dose.…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Patterns of antibody response in humans to the anthrax vaccine adsorbed (AVA) primary (six-dose) series☆

Pittman

Norris

Oro

et al. 2006

Vaccine

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Patterns of antibody response in humans to the anthrax vaccine adsorbed (AVA) primary (six-dose) series☆

Pittman

Norris

Oro

et al. 2006

Vaccine

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“…p38 is not only reported to be phosphorylated and activated to mediate cell apoptosis [7][8][9], but also to have cell protective effects under certain circumstances [10,11]. Why p38 has opposing functions in determining cell fate in different situations remains unclear.…”

Section: Introductionmentioning

confidence: 99%

UV‐induced interaction between p38 MAPK and p53 serves as a molecular switch in determining cell fate

Gong¹,

Liu²,

Xin³

et al. 2010

FEBS Letters

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Edited by Varda RotterKeywords: p38 mitogen-activated protein kinase p53 DNA damage Cell apoptosis Cell survival a b s t r a c t p53 plays a fundamental role in the maintenance of genome integrity after DNA damage, deciding whether cells repair and live, or die. However, the rules that govern its choice are largely undiscovered. Here we show that the functional relationship between p38 and p53 is crucial in defining the cell fate after DNA damage. Upon low dose ultraviolet (UV) radiation, p38 and p53 protect the cells from apoptosis separately. Conversely, they function together to favor apoptosis upon high dose UV exposure. Taken together, a UV-induced, dose-dependent interaction between p38 and p53 acts as a switch to determine cell fate. Structured summary:MINT-8050838: p53 (uniprotkb:P02340) physically interacts (MI:0915) with p38 (uniprotkb:P47811) by anti bait coimmunoprecipitation (MI:0006) MINT-8050948: p53 (uniprotkb:P04637) physically interacts (MI:0915) with p38 (uniprotkb:P47811) by anti tag coimmunoprecipitation (MI:0007)

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“…Survival of activated macrophages critically depends on both NF-kB and the p38 MAP kinase. 28 Work by Michael Karin and co-workers 29 showed that p38 controls the induction of a subset of NF-kBregulated genes by triggering MSK1/2-dependent phosphorylation of CREB, whose binding sites are highly represented in a subset of NF-kB/p38-coregulated genes. The dependence of survival genes on both NF-kB and p38 specifically links macrophage survival to the induction of both pathways and provides a simple paradigm of how parallel signaling events generate a transcriptional cross-talk.…”

Section: Nf-jb Extrinsic Mechanisms Gene-specific Control By Partner mentioning

confidence: 99%

Shaping alternative NF-κB-dependent gene expression programs: new clues to specificity

Natoli

Santa

2006

Cell Death Differ

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The NF-kB/Rel family of sequence-specific transcription factors provides a number of interesting paradigms for combinatorial control of gene regulation. Accumulating evidence indicates that specificity in NF-kB-regulated gene expression is generated at multiple levels, both intrinsic and extrinsic to the NF-kB system. In virtue of these mechanisms, the set of NF-kB-dependent genes induced by alternative stimuli differs significantly. Moreover, mechanisms explaining how specific dimers are linked to the induction of subsets of NF-kB-dependent genes are being clarified. Here, we comment on some of the recent advances in this field and we show the existence of a high level of interconnectivity between extrinsic and intrinsic mechanisms of control. NF-jB Intrinsic MechanismsTemporal control of the NF-jB response and selective gene induction Alternative NF-kB inducers can generate NF-kB activation profiles of different duration: a direct link between temporal control of NF-kB activity and selective gene induction has been recently demonstrated. Hoffmann et al. 1 found that induction of some NF-kB-dependent genes in TNF-stimulated fibroblasts required the presence of NF-kB in the nucleus for a relatively long time (more than 2 h), while many other genes were induced even in response to a single and short cycle of NF-kB activity. In mouse fibroblasts, a short pulse of TNF treatment generates a transient NF-kB response that is terminated in about 1 h by re-synthesis of IkBa. 2 Pulsed TNF treatment was unable to induce a subset of NF-kB targets in wild-type cells, while it was able to induce these genes in cells lacking IkBa in which NF-kB activation in response to the same treatment is sustained. These data provide genetic evidence that alternative kinetics of NF-kB activation directly impact on the transcriptional response. However, the reason why some genes require a long-lasting presence of NF-kB in the nucleus to be activated may be extrinsic to the NF-kB system and related to differences in promoter accessibility to NF-kB (see below). In this light, a short NF-kB pulse will not induce those genes whose remodeling requires a relatively long time to be completed (see below).Following up this work, two recent papers by Covert et al. 3 and Werner et al. 4 showed that stimulus-specific differences in the temporal control of NF-kB activity generate distinct biological responses. While NF-kB activity induced by a pulse of TNFa is rapidly attenuated by negative feedback mechanisms (and in particular IkBa resynthesis), NF-kB activity induced by a pulse of LPS in fibroblasts is sustained due to an autocrine loop dependent on TNFa induction and secretion. TNFa induction in response to LPS requires IRF3, 3 which is activated via the Myd88-independent, Trif-dependent pathway emanating from TLR4. 5 TNFa and possibly additional cytokines are responsible for the late phase of NF-kB activation and NF-kB-dependent gene induction. Therefore, a source of difference between TNF and LPS-induced gene expression programs in mouse fibrobla...

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Macrophage Apoptosis by Anthrax Lethal Factor Through p38 MAP Kinase Inhibition

Cited by 470 publications

References 28 publications

Patterns of antibody response in humans to the anthrax vaccine adsorbed (AVA) primary (six-dose) series☆

Patterns of antibody response in humans to the anthrax vaccine adsorbed (AVA) primary (six-dose) series☆

UV‐induced interaction between p38 MAPK and p53 serves as a molecular switch in determining cell fate

Shaping alternative NF-κB-dependent gene expression programs: new clues to specificity

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