Solution structure of Apaf-1 CARD and its interaction with caspase-9 CARD: A structural basis for specific adaptor/caspase interaction

Zhou, Pei; Chou, James J.; Sanchez-Olea, Roberto; Yuan, Junying; Wagner, Gerhard

doi:10.1073/pnas.96.20.11265

Cited by 133 publications

(116 citation statements)

References 34 publications

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“…Caspase-9 and Apaf-1 bind to each other via their respective NH 2 -terminal CED-3 ('C. elegans Death protein homologue') homologous domains in the presence of cytochrome c and dATP; they have been shown to contain a caspase recruitment domain (CARD) motif that contains several conserved hydrophobic residues (Hofmann et al, 1997;Zhou et al, 1999). Moreover, caspase-9 is negatively regulated by phosphorylation of the Ser-196 residue at the consensus motif 'RRRFSS' (Cardone et al, 1998;Figure 2C).…”

Section: Discussionmentioning

confidence: 99%

“…The arrow denotes the aspartic acid (D) residue after which the cleavage occurs during caspase-9 activation (Srinivasula et al, 1996). Letters coloured red represent the conserved hydrophobic residues of the 1 CARD 97 domain (Hofmann et al, 1997;Zhou et al, 1999). The bold and circled residues indicate the polymorphic sites where amino acid substitution takes place.…”

Section: Casp9 Studies -Expression Analysismentioning

confidence: 99%

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Analyses of apoptotic regulators CASP9 and DFFA at 1P36.2, reveal rare allele variants in human neuroblastoma tumours

et al. 2002

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The genes encoding Caspase-9 and DFF45 have both recently been mapped to chromosome region 1p36.2, that is a region alleged to involve one or several tumour suppressor genes in neuroblastoma tumours. This study presents an update contig of the 'Smallest Region of Overlap of deletions' in Scandinavian neuroblastoma tumours and suggests that DFF45 is localized in the region. The genomic organization of the human DFF45 gene, deduced by in-silico comparisons of DNA sequences, is described for the first time in this paper. In the present study 44 primary tumours were screened for mutation by analysis of the genomic sequences of the genes. In two out of the 44 tumours this detected in the DFFA gene one rare allele variant that caused a non-polar to a polar amino acid exchange in a preserved hydrophobic patch of DFF45. One case was hemizygous due to deletion of the more common allele of this polymorphism. Out of 194 normal control alleles only one was found to carry this variant allele, so in respect of it, no healthy control individual out of 97 was homozygous. Moreover, our RT -PCR expression studies showed that DFF45 is preferably expressed in low-stage neuroblastoma tumours and to a lesser degree in high-stage neuroblastomas. We conclude that although coding mutations of Caspase-9 and DFF45 are infrequent in neuroblastoma tumours, our discovery of a rare allele in two neuroblastoma cases should be taken to warrant further studies of the role of DFF45 in neuroblastoma genetics.

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Section: Discussionmentioning

confidence: 99%

Section: Casp9 Studies -Expression Analysismentioning

confidence: 99%

Analyses of apoptotic regulators CASP9 and DFFA at 1P36.2, reveal rare allele variants in human neuroblastoma tumours

et al. 2002

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“…It is speculated that cytochrome c binding to APAF-1 causes a conformational change in APAF-1 that exposes a caspase recruitment domain for procaspase-9 (Vaughn et al, 1999;Zhou et al, 1999). The complex of APAF-1 and cytochrome c activates the procaspase-9.…”

Section: Mitochondriamentioning

confidence: 99%

Synthetic retinoids as inducers of apoptosis in ovarian carcinoma cell lines

Holmes¹,

Soprano²,

Soprano³

2004

Journal Cellular Physiology

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Apoptosis is also known as programmed cell death. Apoptosis plays an essential role in maintaining normal tissue and cell physiology in multicellular organisms. Clearance of aberrant or pre-cancerous cells occurs through the induction of apoptosis. It has been reported that many tumors and tumor cell lines have dysfunctional apoptosis signaling, causing these tumors to escape immune monitoring and internal cellular control mechanisms. One potential cause of this dysfunctional apoptosis is the tumor suppressor p53, an important regulator of growth arrest and apoptosis that is mutated in over 50% of all cancers. Retinoids have great potential in the areas of cancer therapy and chemoprevention. While some tumor cells are sensitive to the growth inhibitory effects of natural retinoids such as all-trans-retinoic acid (ATRA), many ovarian tumor cells are not. 6-[3-(1-Admantyl)]-4-hydroxyphenyl]-2-naphthalene carboxylic acid (CD437) and fenretinide N-[4-hydroxyphenyl] retinamide (4-HPR) are conformationally restricted synthetic retinoids that induce growth arrest and apoptosis in both ATRA-sensitive and ATRA-resistant ovarian tumor cell lines. Recently, we have identified the molecular pathways of apoptosis induced by treatment of ovarian carcinoma cells with mutated p53 by CD437 and 4-HPR.

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“…Subsequently, activated caspase-9 cleaves downstream caspases such as caspase-3, -6, and -7. In turn, caspase-3 fully processes caspase-9 via a feedback loop leading to amplification of the apoptotic signal and cell degradation (7).…”

Section: Identification Of Pp1␣ As a Caspase-9 Regulator In Il-2 Deprmentioning

confidence: 99%

Identification of PP1α as a Caspase-9 Regulator in IL-2 Deprivation-Induced Apoptosis

Dessauge

Cayla

Albar

et al. 2006

The Journal of Immunology

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One of the mechanisms that regulate cell death is the reversible phosphorylation of proteins. ERK/MAPK phosphorylates caspase-9 at Thr125, and this phosphorylation is crucial for caspase-9 inhibition. Until now, the phosphatase responsible for Thr125 dephosphorylation has not been described. Here, we demonstrate that in IL-2-proliferating cells, phosphorylated serine/threonine phosphatase type 1α (PP1α) associates with phosphorylated caspase-9. IL-2 deprivation induces PP1α dephosphorylation, which leads to its activation and, as a consequence, dephosphorylation and activation of caspase-9 and subsequent dissociation of both molecules. In cell-free systems supplemented with ATP caspase-9 activation is induced by addition of cytochrome c and we show that in this process PP1α is indispensable for triggering caspase-9 as well as caspase-3 cleavage and activation. Moreover, PP1α associates with caspase-9 in vitro and in vivo, suggesting that it is the phosphatase responsible for caspase-9 dephosphorylation and activation. Finally, we describe two novel phosphatase-binding sites different from the previously described PP1α consensus motifs, and we demonstrate that these novel sites mediate the interaction of PP1α with caspase-9.

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Solution structure of Apaf-1 CARD and its interaction with caspase-9 CARD: A structural basis for specific adaptor/caspase interaction

Cited by 133 publications

References 34 publications

Analyses of apoptotic regulators CASP9 and DFFA at 1P36.2, reveal rare allele variants in human neuroblastoma tumours

Analyses of apoptotic regulators CASP9 and DFFA at 1P36.2, reveal rare allele variants in human neuroblastoma tumours

Synthetic retinoids as inducers of apoptosis in ovarian carcinoma cell lines

Identification of PP1α as a Caspase-9 Regulator in IL-2 Deprivation-Induced Apoptosis

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