Caspases, IAPs and Smac/DIABLO: mechanisms from structural biology

Shiozaki, Eric N.; Shi, Yigong

doi:10.1016/j.tibs.2004.07.003

Cited by 205 publications

(187 citation statements)

References 72 publications

Supporting

Mentioning

181

Contrasting

Unclassified

Order By: Relevance

“…An increase in Diablo might thus be an indication that under cell death stimuli, apoptosis is highly favoured. The signals which promote increases in Diablo are not known, but as a component of the mitochondrion it is likely associated with the intrinsic apoptotic pathway, responding to cellular damage (Shiozaki and Shi, 2004), and Diablo mimetics have recently been shown to increase the susceptibility of diseased cells to apoptosis-inducing drugs (Fulda et al, 2002) (Bank et al, 2008). The pattern and magnitude of expression changes in flounder liver indicate that Diablo, and the pathways to which it belongs are worthy of further investigation, with the prospect of developing more relevant environmental biomarkers.…”

Section: Discussionmentioning

confidence: 99%

Hepatic gene expression in flounder chronically exposed to multiply polluted estuarine sediment: Absence of classical exposure ‘biomarker’ signals and induction of inflammatory, innate immune and apoptotic pathways

et al. 2010

View full text Add to dashboard Cite

The effects of chronic long term exposure to multiply-polluted environments on fish are not well understood, but environmental surveys suggest that such exposure may cause a variety of pathologies, including cancers. Transcriptomic profiling has recently been used to assess gene expression in European flounder (Platichthys flesus) living in several polluted and clean estuaries. However, the gene expression changes detected were not unequivocally elicited by pollution, most likely due to the confounding effects of natural estuarine ecosystem variables. In this study flounder from an uncontaminated estuary were held on clean or polluted sediments in mesocosms, allowing control of variables such as salinity, temperature, and diet. After 7 months flounder were removed from each mesocosm and hepatocytes prepared from fish exposed to clean or polluted sediments. The hepatocytes were treated with benzo(a)pyrene (BAP), estradiol (E2), copper, a mixture of these three, or with the vehicle DMSO. A flounder cDNA microarray was then used to measure hepatocyte transcript abundance after each treatment. The results show that long term chronic exposure to a multiply-polluted sediment causes increases in the expression of mRNAs coding for proteins of the endogenous apoptotic program, of innate immunity and inflammation. Contrary to expectation, the expression of mRNAs which are commonly used as biomarkers of environmental exposure to particular contaminants were not changed, or were changed contrary to expectation. However, acute treatment of hepatocytes from flounder from both clean and polluted sediments with BAP or E2 caused the expected changes in the expression of these biomarkers. Thus transcriptomic analysis of flounder exposed long-term to chronic pollution causes a different pattern of gene expression than in fish acutely treated with single chemicals, and reveals novel potential biomarkers of environmental contaminant exposure. These novel biomarkers include Diablo, a gene involved in apoptotic pathways and highly differentially regulated by both chronic and acute exposure to multiple pollutants.

show abstract

Section: Discussionmentioning

confidence: 99%

Hepatic gene expression in flounder chronically exposed to multiply polluted estuarine sediment: Absence of classical exposure ‘biomarker’ signals and induction of inflammatory, innate immune and apoptotic pathways

et al. 2010

View full text Add to dashboard Cite

show abstract

“…3 All animal cells contain them, but their activity is normally prevented by the inhibitor of apoptosis proteins (IAPs). 4,5 Thus, a key regulatory step in apoptosis is the control of IAP function.…”

mentioning

confidence: 99%

A dp53/JNK-dependant feedback amplification loop is essential for the apoptotic response to stress in Drosophila

2011

View full text Add to dashboard Cite

Programmed cell death (apoptosis) is a conserved process aimed to eliminate unwanted cells. The key molecules are a group of proteases called caspases that cleave vital proteins, which leads to the death of cells. In Drosophila, the apoptotic pathway is usually represented as a cascade of events in which an initial stimulus activates one or more of the proapoptotic genes (hid, rpr, grim), which in turn activate caspases. In stress-induced apoptosis, the dp53 (Drosophila p53) gene and the Jun N-terminal kinase (JNK) pathway function upstream in the activation of the proapoptotic genes. Here we demonstrate that dp53 and JNK also function downstream of proapoptotic genes and the initiator caspase Dronc (Drosophila NEDD2-like caspase) and that they establish a feedback loop that amplifies the initial apoptotic stimulus. This loop plays a critical role in the apoptotic response because in its absence there is a dramatic decrease in the amount of cell death after a pulse of the proapoptotic proteins Hid and Rpr. Thus, our results indicate that stress-induced apoptosis in Drosophila is dependant on an amplification loop mediated by dp53 and JNK. Furthermore, they also demonstrate a mechanism of mutual activation of proapoptotic genes.

show abstract

“…In addition, this apoptotic pathway can be regulated downstream of cytochrome c release by caspase inhibitor proteins such as XIAP (23). The activity of XIAP may be controlled by release of other factors such as Smac/Diablo from mitochondria (24). Components of the pathway such as caspase-9 (25,26) and XIAP (27) are also regulated post-translationally through phosphorylation by protein kinases activated by signaling pathways.…”

mentioning

confidence: 99%

Protein Kinase A Regulates Caspase-9 Activation by Apaf-1 Downstream of Cytochrome c

Martin

Allan

Lickrish

et al. 2005

Journal of Biological Chemistry

View full text Add to dashboard Cite

The cyclic AMP signal transduction pathway modulates apoptosis in diverse cell types, although the mechanism is poorly understood. A critical component of the intrinsic apoptotic pathway is caspase-9, which is activated by Apaf-1 in the apoptosome, a large complex assembled in response to release of cytochrome c from mitochondria. Caspase-9 cleaves and activates effector caspases, predominantly caspase-3, resulting in the demise of the cell. Here we identified a distinct mechanism by which cyclic AMP regulates this apoptotic pathway through activation of protein kinase A. We show that protein kinase A inhibits activation of caspase-9 and caspase-3 downstream of cytochrome c in Xenopus egg extracts and in a human cell-free system. Protein kinase A directly phosphorylates human caspase-9 at serines 99, 183, and 195. However, mutational analysis demonstrated that phosphorylation at these sites is not required for the inhibitory effect of protein kinase A on caspase-9 activation. Importantly, protein kinase A inhibits cytochrome c-dependent recruitment of procaspase-9 to Apaf-1 but not activation of caspase-9 by a constitutively activated form of Apaf-1. These data indicate that extracellular signals that elevate cyclic AMP and activate protein kinase A may suppress apoptosis by inhibiting apoptosome formation downstream of cytochrome c release from mitochondria.

show abstract

Caspases, IAPs and Smac/DIABLO: mechanisms from structural biology

Cited by 205 publications

References 72 publications

Hepatic gene expression in flounder chronically exposed to multiply polluted estuarine sediment: Absence of classical exposure ‘biomarker’ signals and induction of inflammatory, innate immune and apoptotic pathways

Hepatic gene expression in flounder chronically exposed to multiply polluted estuarine sediment: Absence of classical exposure ‘biomarker’ signals and induction of inflammatory, innate immune and apoptotic pathways

A dp53/JNK-dependant feedback amplification loop is essential for the apoptotic response to stress in Drosophila

Protein Kinase A Regulates Caspase-9 Activation by Apaf-1 Downstream of Cytochrome c

Contact Info

Product

Resources

About