Molecular chaperones as regulators of cell death

Hishiya, Akinori; Takayama, Shinichi

doi:10.1038/onc.2008.314

Cited by 44 publications

(33 citation statements)

References 229 publications

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“…Here, we compare MMEC with MGEC protein expression profiles, and identify four constantly overexpressed proteins in MMECs: filamin A (FLNA), vimentin (VIM), a-crystallin B (CRYAB) and 14-3-3z/d protein (YWHAZ) not yet previously correlated with overangiogenic activity. FLNA and VIM are cytoskeletal proteins governing cell adhesion and spreading (Kim et al, 2010), CRYAB is a small heat shock protein (HSP) with antiapoptotic activity (Hishiya and Takayama, 2008) and YWHAZ is a 'scaffold' protein implicated in the regulation of a large spectrum of signaling pathways (Morrison, 2009). We demonstrate that these proteins are essential for MMEC adhesion, migration and enhanced angiogenesis, and that they may be envisaged as targets for antiangiogenic purposes in MM patients.…”

Section: Introductionmentioning

confidence: 92%

Four proteins governing overangiogenic endothelial cell phenotype in patients with multiple myeloma are plausible therapeutic targets

et al. 2011

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Bone marrow (BM) angiogenesis has an important role in the initiation and progression of multiple myeloma (MM). We looked at novel mechanisms of vessel formation in patients with MM through a comparative proteomic analysis between BM endothelial cells (ECs) of patients with active MM (MMECs) and ECs of patients with monoclonal gammopathy of undetermined significance (MGECs) and of subjects with benign anemia (normal ECs). Four proteins were found overexpressed in MMECs: filamin A, vimentin, a-crystallin B and 14-3-3f/d protein, not yet linked to overangiogenic phenotype. These proteins gave a typical distribution in the BM of MM patients and in MMECs versus MGECs, plausibly according to a different functional state. Their expression was enhanced by vascular endothelial growth factor, fibroblast growth factor 2, hepatocyte growth factor and MM plasma cell conditioned medium in step with enhancement of MMEC angiogenesis. Their silencing RNA knockdown affected critical MMEC angiogenesis-related functions, such as spreading, migration and tubular morphogenesis. A gradual stabilization of 14-3-3f/d protein was observed, with transition from normal ECs to MGECs and MMECs that may be a critical step for the angiogenic switch in MMECs and maintenance of the cell overangiogenic phenotype. These proteins were substantially impacted by anti-MM drugs, such as bortezomib, lenalidomide and panobinostat. Results suggest that these four proteins could be new targets for the antiangiogenic management of MM patients.

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Section: Introductionmentioning

confidence: 92%

Four proteins governing overangiogenic endothelial cell phenotype in patients with multiple myeloma are plausible therapeutic targets

et al. 2011

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“…In general, misfolded or unfolded proteins are either refolded by molecular chaperones or degraded immediately by the ubiquitin proteasome system (UPS) (Hishiya and Takayama, 2008;Muchowski et al, 2000), which is known as an intrinsic protein quality control. We hypothesized that SVBP might contribute to the quality control of VASH1 protein in ECs.…”

Section: Svbp Prevents Ubiquitylation Of Vash1mentioning

confidence: 99%

Isolation of a small vasohibin-binding protein (SVBP) and its role in vasohibin secretion

Suzuki

Kobayashi

Miyashita

et al. 2010

Journal of Cell Science

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SummaryUpon stimulation with angiogenic factors, vascular endothelial cells (ECs) secrete a negative-feedback regulator of angiogenesis, vasohibin-1 (VASH1). Because VASH1 lacks a classical signal sequence, it is not clear how ECs secrete VASH1. We isolated a small vasohibin-binding protein (SVBP) composed of 66 amino acids. The level of Svbp mRNA was relatively high in the bone marrow, spleen and testes of mice. In cultured ECs, Vash1 mRNA was induced by VEGF, and Svbp mRNA was expressed constitutively. The interaction between VASH1 and SVBP was confirmed using the BIAcore system and immunoprecipitation analysis. Immunocytochemical analysis revealed that SVBP colocalized with VASH1 in ECs. In polarized epithelial cells, SVBP accumulated on the apical side, whereas VASH1 was present throughout the cells and partially colocalized with SVBP. Transfection of SVBP enhanced VASH1 secretion, whereas knockdown of endogenous SVBP markedly reduced VASH1 secretion. SVBP increased the solubility of VASH1 protein in detergent solution and inhibited the ubiquitylation of VASH1 protein. Moreover, co-transfection of SVBP significantly augmented the inhibitory effect of VASH1 on EC migration. These results indicate that SVBP acts as a secretory chaperone for VASH1 and contributes to the anti-angiogenic activity of VASH1.

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“…sHSPs interact with a lot of essential cellular structures. Hence, sHSPs seem to be implicated in a wide variety of human diseases (23,32,54,55).…”

mentioning

confidence: 99%

The Small Heat Shock Protein ODF1/HSPB10 Is Essential for Tight Linkage of Sperm Head to Tail and Male Fertility in Mice

Yang

Meinhardt

Zhang

et al. 2012

Molecular and Cellular Biology

131

122

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Sperm motility and hence male fertility strictly depends on proper development of the sperm tail and its tight anchorage to the head. The main protein of sperm tail outer dense fibers, ODF1/HSPB10, belongs to the family of small heat shock proteins that function as molecular chaperones. However, the impact of ODF1 on sperm tail formation and motility and on male fecundity is unknown. We therefore generated mutant mice in which the Odf1 gene was disrupted. Heterozygous mutant male mice are fertile while sperm motility is reduced, but Odf1-deficient male mice are infertile due to the detachment of the sperm head. Although headless tails are somehow motile, transmission electron microscopy revealed disturbed organization of the mitochondrial sheath, as well as of the outer dense fibers. Our results thus suggest that ODF1, besides being involved in the correct arrangement of mitochondrial sheath and outer dense fibers, is essential for rigid junction of sperm head and tail. Loss of function of ODF1, therefore, might account for some of the cases of human infertility with decapitated sperm heads. In addition, since sperm motility is already affected in heterozygous mice, impairment of ODF1 might even account for some cases of reduced fertility in male patients.

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Molecular chaperones as regulators of cell death

Cited by 44 publications

References 229 publications

Four proteins governing overangiogenic endothelial cell phenotype in patients with multiple myeloma are plausible therapeutic targets

Four proteins governing overangiogenic endothelial cell phenotype in patients with multiple myeloma are plausible therapeutic targets

Isolation of a small vasohibin-binding protein (SVBP) and its role in vasohibin secretion

The Small Heat Shock Protein ODF1/HSPB10 Is Essential for Tight Linkage of Sperm Head to Tail and Male Fertility in Mice

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