Functional Role of Death-associated Protein 3 (DAP3) in Anoikis

Miyazaki, Tatsuya; Shen, Min; Fujikura, Daisuke; Tosa, Noriko; Kim, Hyung‐Ryong; Kawa, Shigeyuki; Uede, Toshimitsu; Reed, John C.

doi:10.1074/jbc.m408101200

Cited by 55 publications

(57 citation statements)

References 31 publications

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“…Unlike DCC, UNC5Hs and RET, which promote apoptosis via direct association with caspase 9 and subsequent cleavage and liberation of a cytoslolic addiction/dependence domain, unligated integrins initiate a caspase 8-dependent pathway. 61,63,[66][67][68] The colocalization and coprecipitation of caspase 8 with unligated integrins has been shown. 58,61 However, pull-down type studies using recombinant GST-integrin cytosolic domains suggest that this interaction is not a simple 1 : 1 stoichiometric binding, or alternatively results from an indirect interaction with a third protein in the integrin-associated complex (unpublished observations).…”

Section: Unligated Integrins Recruit Caspasementioning

confidence: 95%

Integrins as a distinct subtype of dependence receptors

Stupack

2005

Cell Death Differ

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In the absence of their cognate ligand, dependence receptors trigger programmed cell death. This function is the defining feature of dependence receptors, which include members of several different protein families. The integrins are a family of heterodimeric receptors for extracellular matrix (ECM) proteins, mediating cell anchorage and migration. Integrins share characteristics with dependence receptors, and integrin binding to substrate ECM ligands is essential for cell survival. Although integrins do not conform in all characteristics to the established definitions of dependence receptors, alterations in the expression of integrins and their ligands during physiological and pathological events, such as wound healing, angiogenesis and tumorigenesis, do regulate cell fate in a ligand-dependent manner. This biosensory function of integrins fits well with our current concept of dependence receptor action, and thus integrins may rightly be considered to comprise a distinct subclass of dependence receptor.

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Section: Unligated Integrins Recruit Caspasementioning

confidence: 95%

Integrins as a distinct subtype of dependence receptors

Stupack

2005

Cell Death Differ

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“…DAP3 is associated with anoikis (cell death following detachment from substrate) [30], but most cancer cells are not subject to this mechanism. Thus, loss of this gene would be expected to be associated with progression.…”

Section: Discussionmentioning

confidence: 99%

Template-driven gene selection procedure

Knowlton

Dozmorov

Kyker

et al. 2006

IEE Proc. Syst. Biol.

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The hierarchical clustering and statistical techniques usually used to analyze microarray data do not inherently represent the underlying biology. Herein we present a hybrid approach involving characteristics of both supervised and unsupervised learning. This approach is based on template matching in which the interaction of the variables of inherent malignancy and the ability to express the malignant phenotype are modelled. Immortalized normal urothelial cells and bladder cancer cells of different malignancy were grown in conventional two-dimensional tissue culture and in three dimensions on extracellular matrices that were either permissive or restrictive for expression of the malignant phenotype. The transcriptome represents the effects of two variables--inherent malignancy and the modulatory effect of extracellular matrix. By assigning values to each of the biological variables of inherent malignancy and the ability to express the malignant phenotype, a template was constructed that encapsulated the interaction between them. Gene expression correlating both positively and negatively with the template were observed, but when iterative correlations were carried out, the different models for the template converged to the same actual template. A subset of 21 genes was identified that correlated with two a priori models or an optimized model above the 95% confidence limits identified in a bootstrap resampling with 5,000 permutations of the data set. The correlation coefficients of expression of several genes were > 0.8. Analysis of upstream transcriptional regulatory elements (TREs) confirmed these genes were not a randomly selected set of genes. Several TREs were identified as significantly over-expressed in the sample of 20 genes for which TREs were identified, and the high correlations of several genes were consistent with transcriptional co-regulation. We suggest the template method can be used to identify a unique set of genes for further investigation. KeywordsBladder cancer; phenotype; transcriptomics; extracellular matrix; malignancy * This work was supported in part by NIH grants CA75322 (REH), DK 069808 (REH) and P20 RR1557, P20 RR17703, and P20 RR16478 (MBC) and by a grant from Cook Biotech (REH).

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“…It has been reported that mitochondrial DAP3 regulates cellular senescence though an oxidative stress response [8]. Moreover, DAP3 is reportedly phosphorylated in an Akt-dependent manner, correlating with the suppression of DAP3-facilitated apoptosis in anoikis [9], and IFN-β promoter stimulator 1 (IPS-1) binds DAP3, resulting in induced anoikis by caspase activation [10]. Although the accumulating evidence shows that DAP3 plays roles in apoptosis induction, the role of DAP3 in thymocyte development is still unknown.…”

Section: Death-associated Protein 3 (Dap3) Is Ubiquitously Expressed mentioning

confidence: 94%

Critical function of death-associated protein 3 in T cell receptor-mediated apoptosis induction

Tosa

Iwai

Tanaka

et al. 2010

Biochemical and Biophysical Research Communications

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Death associated protein 3 (DAP3) is crucial for promoting apoptosis induced by various stimulations. This report demonstrates that DAP3 is also important for T cell receptor (TCR)-mediated apoptosis induction in immature thymocytes. Enforced expression of DAP3 accelerated the negative selection in developing thymocytes, using the reaggregate thymus organ culture system. In addition, expression of DAP3 accelerated TCR-mediated apoptosis induction in DO11.10 cells. We also demonstrated that DAP3 translocates into the nucleus during TCR-mediated apoptosis in a Nur77 dependent manner. It is concluded that DAP3 is critical for TCR-mediated induction of apoptosis at the downstream of Nur77.Keywords: apoptosis / death associated protein 3 / negative selection / Nur77 / T cell receptor / Abbreviations: IFN, interferon; NR box, nuclear receptor-interacting domain; WT, wild-type; DN, dominant-negative form; RTOC, reaggregate thymus organ culture; FADD, FAS-associated death domain protein

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Functional Role of Death-associated Protein 3 (DAP3) in Anoikis

Cited by 55 publications

References 31 publications

Integrins as a distinct subtype of dependence receptors

Integrins as a distinct subtype of dependence receptors

Template-driven gene selection procedure

Critical function of death-associated protein 3 in T cell receptor-mediated apoptosis induction

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