Identification of a Cytokine-induced Antiapoptotic Molecule Anamorsin Essential for Definitive Hematopoiesis

Shibayama, Hirohiko; Takai, Emi; Matsumura, Itaru; Kouno, Michiyoshi; Morii, Eiichi; Kitamura, Yukihiko; Takeda, Junji

doi:10.1084/jem.20031858

Cited by 113 publications

(123 citation statements)

References 48 publications

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“…Although the molecular targets of the electron transfer flow generated by this protein-protein complex are not yet defined, suggestions for the targets of the electron flow include the conversion of the sulfur of cysteine (formally S 0 ) to the sulfide (S 2− ) present in Fe/S clusters and/or the reductive coupling of two [2Fe-2S] clusters to form a [4Fe-4S] cluster (13). This nondissociative electron transfer process might also rationalize how anamorsin regulates cell survival/death mechanisms in human cells (35) and why a stable Dre2-Tah18 interaction is essential for yeast viability (16). Indeed, the disruption of the stable interaction between anamorsin and Ndor1 might provoke the interruption of the electron flow between the two proteins within the cell and, as a result of that, its essential function for cellular survival is abolished and consequently cell death mechanisms might be activated.…”

Section: Discussionmentioning

confidence: 99%

Molecular view of an electron transfer process essential for iron–sulfur protein biogenesis

Banci

Bertini

Calderone

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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Biogenesis of iron-sulfur cluster proteins is a highly regulated process that requires complex protein machineries. In the cytosolic iron-sulfur protein assembly machinery, two human key proteins-NADPH-dependent diflavin oxidoreductase 1 (Ndor1) and anamorsinform a stable complex in vivo that was proposed to provide electrons for assembling cytosolic iron-sulfur cluster proteins. The Ndor1-anamorsin interaction was also suggested to be implicated in the regulation of cell survival/death mechanisms. In the present work we unravel the molecular basis of recognition between Ndor1 and anamorsin and of the electron transfer process. This is based on the structural characterization of the two partner proteins, the investigation of the electron transfer process, and the identification of those protein regions involved in complex formation and those involved in electron transfer. We found that an unstructured region of anamorsin is essential for the formation of a specific and stable protein complex with Ndor1, whereas the C-terminal region of anamorsin, containing the [2Fe-2S] redox center, transiently interacts through complementary charged residues with the FMN-binding site region of Ndor1 to perform electron transfer. Our results propose a molecular model of the electron transfer process that is crucial for understanding the functional role of this interaction in human cells.Fe/S protein maturation | CIAPIN1 domain | diflavin reductase I ron-sulfur clusters (ISCs) are ancient inorganic cofactors that are crucial for many protein functions in eukaryotic and bacterial cells (1-3). The clusters are composed of inorganic sulfide and ferric/ ferrous iron atoms, the latter being preferentially coordinated by cysteinyl residues (4-6). Because inorganic sulfide and ferrous/ferric iron atoms are toxic in vivo, biosynthesis of ISC proteins within cells is a highly regulated process that requires complex protein machineries for the mobilization of Fe and S atoms from appropriate sources, for their assembly into ISC forms and their final delivery to the recipient proteins (7-9). Three distinct protein machineries are operative and essential in the (nonplant) eukaryotic cells for the biogenesis of ISC proteins: (i) the ISC assembly machinery in the mitochondrial matrix, (ii) the ISC export machinery located in the mitochondrial intermembrane space, and (iii) the cytosolic iron-sulfur protein assembly (CIA) machinery.The CIA machinery comprises several proteins (10, 11), among which one named Dre2 has been recently identified in yeast (12). The C-terminal domain of Dre2 (residues 228-348) is able to bind two ISCs, a [2Fe-2S] and a [4Fe-4S] (12, 13). The [2Fe-2S] cluster of Dre2 receives electrons from a cytosolic diflavin reductase, termed Tah18 (13), which contains a FAD and a FMN prosthetic group, respectively, bound in two distinct structural domains, to accept electrons from NADPH (14). Dre2 and Tah18 are protein partners forming a stable complex in vivo (13, 15). The C-terminal region of Dre2 (residues 173-348) is fundamenta...

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Section: Discussionmentioning

confidence: 99%

Molecular view of an electron transfer process essential for iron–sulfur protein biogenesis

Banci

Bertini

Calderone

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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“…Cytokine-induced apoptosis inhibitor 1 (CIAPIN1) is an important regulator of cell apoptosis. It has a significant inhibitory effect on multiple links in cell apoptotic pathways and a positive regulatory effect on Ras and other survival signaling pathways, thus promoting cell survival and proliferation (Shibayama et al, 2004). In recent years, many studies on the relationship www.intechopen.com between CIAPIN1 and tumor formation showed that CIAPIN1 expression was increased significantly in HCC, gastric cancer and other malignant tumor tissues (Ida et al, 2007;.…”

Section: Cytokine-induced Apoptosis-inhibiting Moleculementioning

confidence: 99%

RNA Interference for Tumor Therapy

Xia¹,

Ni²

2012

Biomedicine

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Section: Introductionmentioning

confidence: 99%

“…4 Additionally, CIAPIN1 protects Ba/F3 cells against etoposide, gamma radiation and stauroporine in vitro. 4 In addition, our previous study confirmed that CIAPIN1 was upregulated in several multidrug resistance cancer cell lines and might have a role in mediating multidrug resistance of cancer cells. 5,6 Furthermore, CIAPIN1 expression was correlated with malignant phenotype of several cancers such as gastric cancer, liver cancer, esophagus cancer, lung cancer, lymphoma and kidney cancer, 7--15 which strongly suggested that CIAPIN1 might be an important protein involving in tumorigenicity and carcinogenesis.…”

Section: Introductionmentioning

confidence: 99%

Overexpression of CIAPIN1 inhibited pancreatic cancer cell proliferation and was associated with good prognosis in pancreatic cancer

Chen

et al. 2012

Cancer Gene Ther

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Cytokine-induced antiapoptotic molecule (CIAPIN1), a newly identified apoptosis inhibitor, has been found to participate in the process of proliferation and tumorigenicity for several cancers. The aim of this study was to evaluate the prognostic value of CIAPIN1 in pancreatic cancer and to probe its function in pancreatic carcinogenesis. We found that CIAPIN1 protein was absent or reduced in pancreatic cancer cell lines. There was also a loss or decrease in CIAPIN1 expression in 118 cases of pancreatic cancer tissues as compared with that in 82 cases of normal pancreatic tissues. In a Cox proportional hazards model, CIAPIN1 expression independently predicted better survival (Po0.0001). Adenoviral-mediated restoration of CIAPIN1 expression greatly repressed the proliferation of pancreatic cancer cell in vitro and suppressed the tumorigenicity of pancreatic cancer cell in Balb/ c nude mice. Our data also revealed that inhibition of pancreatic cancer cells proliferation by enforcing CIAPIN1 expression at least partly through delaying cell cycle progression and inducing cell apoptosis. In summary, our work revealed a novel function of CIAPIN1, which might possibly be used as an independent prognostic factor and a potential therapeutic target for pancreatic cancer.

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Identification of a Cytokine-induced Antiapoptotic Molecule Anamorsin Essential for Definitive Hematopoiesis

Cited by 113 publications

References 48 publications

Molecular view of an electron transfer process essential for iron–sulfur protein biogenesis

Molecular view of an electron transfer process essential for iron–sulfur protein biogenesis

RNA Interference for Tumor Therapy

Overexpression of CIAPIN1 inhibited pancreatic cancer cell proliferation and was associated with good prognosis in pancreatic cancer

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