共查询到20条相似文献,搜索用时 15 毫秒
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De Zio D Ferraro E D'Amelio M Simoni V Bordi M Soroldoni D Berghella L Meyer BI Cecconi F 《Cellular and molecular life sciences : CMLS》2008,65(11):1780-1790
Fas-associated factor 1 (Faf1) has been described as a Fas-binding pro-apoptotic protein and as a component of the death-inducing signaling complex (DISC) in Fas-mediated apoptosis. Faf1 is able to potentiate Fas-induced apoptosis in several cell lines, although its specific functions are still not clear. Here we show that Faf1 is highly expressed in several areas of the developing telencephalon. Its expression pattern appears to be dynamic at different embryonic stages and to be progressively confined within limited territories. To decipher the specific role of Faf1 in developing brain, we used cDNA over-expression and mRNA down-regulation experiments to modulate Faf1 expression in telencephalic neural precursor cells, and we showed that in neural cell death Faf1 acts as a Fas-independent apoptotic enhancer. Moreover, we found that Faf1 protein level is down-regulated during apoptosis in a caspase- and Apaf1-dependent manner. 相似文献
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Z. Zhang V. Majava A. Greffier R. L. Hayes P. Kursula K. K. W. Wang 《Cellular and molecular life sciences : CMLS》2009,66(3):526-536
Collapsin response mediator protein-2 (CRMP-2) plays a crucial role in axonal guidance and neurite outgrowth during neural
development and regeneration. We have studied the interaction between calmodulin (CaM) and CRMP-2 and how Ca2+/CaM binding modulates the biological functions of CRMP-2. We have shown that CRMP-2 binds to CaM directly in a Ca2+-dependent manner. The CaM binding site of CRMP-2 is proposed to reside in the last helix of the folded domain, and in line
with this, a synthesized peptide representing this helix bound to CaM. In addition, CaM binding inhibits a homotetrameric
assembly of CRMP-2 and attenuates calpainmediated CRMP-2 proteolysis. Furthermore, a CaM antagonist reduces the number and
length of process induced by CRMP-2 overexpression in HEK293 cells. Take together, our data suggest that CRMP-2 is a novel
CaM-binding protein and that CaM binding may play an important role in regulating CRMP-2 functions.
Received 26 June 2008; received after revision 18 November 2008; accepted 24 November 2008 相似文献
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Fajka-Boja R Blaskó A Kovács-Sólyom F Szebeni GJ Tóth GK Monostori E 《Cellular and molecular life sciences : CMLS》2008,65(16):2586-2593
Mammalian galectin-1 (Gal-1), a beta-galactoside-binding lectin has a prominent role in regulating cell adhesion, cell growth and immune responses. Downregulation of these biological functions may occur via internalization of Gal-1. In the present study we have investigated the mechanism and possible mediator(s) of Gal-1 endocytosis. We show that internalization occurs at a temperature higher than 22 degrees C in an energy dependent fashion. After one hour incubation Gal-1 localizes in the Golgi system within the cells, and then disappears without accumulation in degradation compartments, such as lysosomes. Based on their strong intracellular co-localization, two glycoconjugates, GM1 ganglioside and CD7 are implicated in the sorting of internalized Gal-1 into Golgi. Other known Gal-1 binding glycoproteins on T cells (CD2, CD3, CD43 and CD45) do not cointernalize with the lectin. Internalization of Gal-1 depends on its lectin activity and follows dual pathways involving clathrin-coated vesicles and raft-dependent endocytosis. 相似文献
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V. Le Fourn K. Gaplovska-Kysela B. Guhl R. Santimaria C. Zuber J. Roth 《Cellular and molecular life sciences : CMLS》2009,66(8):1434-1445
Little is known about the fate of machinery proteins of the protein quality control and endoplasmic reticulum(ER)-associated
degradation (ERAD). We investigated the degradation of the ERAD component EDEM1, which directs overexpressed misfolded glycoproteins
to degradation. Endogenous EDEM1 was studied since EDEM1 overexpression not only resulted in inappropriate occurrence throughout
the ER but also caused cytotoxic effects. Proteasome inhibitors had no effect on the clearance of endogenous EDEM1 in non-starved
cells. However, EDEM1 could be detected by immunocytochemistry in autophagosomes and biochemically in LC3 immuno-purified
autophagosomes. Furthermore, influencing the lysosome-autophagy pathway by vinblastine or pepstatin A/E64d and inhibiting
autophagosome formation by 3-methyladenine or ATGs short interfering RNA knockdown stabilized EDEM1. Autophagic degradation
involved removal of cytosolic Triton X-100-insoluble deglycosylated EDEM1, but not of EDEM1-containing ER cisternae. Our studies
demonstrate that endogenous EDEM1 in cells not stressed by the expression of a transgenic misfolded protein reaches the cytosol
and is degraded by basal autophagy.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.
Received 15 January 2009; received after revision 16 February 2009; accepted 17 February 2009
V. Le Fourn, K. Gaplovska-Kysela: These authors equally contributed to this work. 相似文献
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Porcelli AM Ghelli A Iommarini L Mariani E Hoque M Zanna C Gasparre G Rugolo M 《Cellular and molecular life sciences : CMLS》2008,65(18):2943-2951
Human thyroid carcinoma XTC.UC1 cells harbor a homoplasmic frameshift mutation in the MT-ND1 subunit of respiratory complex
I. When forced to use exclusively oxidative phosphorylation for energy production by inhibiting glycolysis, these cells triggered
a caspase-independent cell death pathway, which was associated to a significant imbalance in glutathione homeostasis and a
cleavage of the actin cytoskeleton. Overexpression of the anti-apoptotic Bcl-2 protein significantly increased the level of
endogenous reduced glutathione, thus preventing its oxidation after the metabolic stress. Furthermore, Bcl-2 completely inhibited
actin cleavage and increased cell adhesion, but was unable to improve cellular viability. Similar effects were obtained when
XTC.UC1 cells were incubated with exogenous glutathione. We hence propose that Bcl-2 can safeguard cytoskeletal stability
through an antioxidant function.
Received 28 May 2008; received after revision 8 July 2008; accepted 29 July 2008 相似文献
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Wang Y Guan X Fok KL Li S Zhang X Miao S Zong S Koide SS Chan HC Wang L 《Cellular and molecular life sciences : CMLS》2008,65(23):3822-3829
Rhomboid family members are widely conserved and found in all three kingdoms of life. They are serine proteases and serve
important regulatory functions. In the present study, a novel gene highly expressed in the testis, RHBDD1, is shown to be
a new member of the Rhomboid family, participating in the cleavage of BIK, a proapoptotic member of the Bcl-2 family. The
RHBDD1-involved proteolytic modification is upstream of the BIK protein degradation pathway. Mutagenesis studies show that
the amino acid residues glycine142 and serine144 of RHBDD1 are crucial for its activity in cleaving BIK at a site located
in the transmembrane region. Overexpression or knock-down of RHBDD1 in HEK 293T cells can reduce or enhance BIK-mediated apoptosis,
respectively. The present findings suggest that, by acting as a serine protease, RHBDD1 modulates BIK-mediated apoptotic activity.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.
Received 31 July 2008; received after revision 16 September 2008; accepted 19 September 2008 相似文献
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The multifunctional roles of the four-and-a-half-LIM only protein FHL2 总被引:14,自引:1,他引:14
Johannessen M Møller S Hansen T Moens U Van Ghelue M 《Cellular and molecular life sciences : CMLS》2006,63(3):268-284
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D. E. Dye S. Karlen B. Rohrbach O. Staub L. R. Braathen K. A. Eidne D. R. Coombe 《Cellular and molecular life sciences : CMLS》2009,66(4):681-696
hShroom1 (hShrm1) is a member of the Apx/Shroom (Shrm) protein family and was identified from a yeast two-hybrid screen as
a protein that interacts with the cytoplasmic domain of melanoma cell adhesion molecule (MCAM). The characteristic signature
of the Shrm family is the presence of a unique domain, ASD2 (Apx/Shroom domain 2). mRNA analysis suggests that hShrm1 is expressed
in brain, heart, skeletal muscle, colon, small intestine, kidney, placenta and lung tissue, as well a variety of melanoma
and other cell lines. Co-immunoprecipitation and bioluminescence resonance energy transfer (BRET) experiments indicate that
hShrm1 and MCAM interact in vivo and by immunofluorescence microscopy some co-localization of these proteins is observed. hShrm1 partly co-localises with
β-actin and is found in the Triton X-100 insoluble fraction of melanoma cell extracts. We propose that hShrm1 is involved
in linking MCAM to the cytoskeleton.
D. E. Dye, S. Karlen: These authors contributed equally to this work.
Received 09 October 2008; received after revision 23 November 2008; accepted 09 December 2008 相似文献
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A. C. S. Souza S. Azoubel K. C. S. Queiroz M. P. Peppelenbosch C. V. Ferreira 《Cellular and molecular life sciences : CMLS》2009,66(7):1140-1153
Reversible tyrosine phosphorylation is a key posttranslational regulatory modification of proteins in all eukaryotic cells
in normal and pathological processes. Recently a pivotal janus-faced biological role of the low molecular weight protein tyrosine
phosphatase (LMWPTP) has become clear. On the one hand this enzyme is important in facilitating appropriate immune responses
towards infectious agents, on the other hand it mediates exaggerated inflammatory responses toward innocuous stimuli. The
evidence that LMWPTP plays a role in oncological processes has added a promising novel angle. In this review we shall focus
on the regulation of LMWPTP enzymatic activity of signaling pathways of different immunological cells, the relation between
genetic polymorphism of LMWPTP and predisposition to some type of inflammatory disorders and the contribution of this enzyme
to cancer cell onset, growth and migration. Therefore, the LMWPTP is an interesting target for pharmacological intervention,
thus modifying both inappropriate cellular immune responses and cancer cell aggressiveness.
Received 15 August 2008; received after revision 06 October 2008; accepted 14 October 2008 相似文献
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Interaction of galectin-1 with caveolae induces mouse embryonic stem cell proliferation through the Src, ERas, Akt and mTOR signaling pathways 总被引:1,自引:0,他引:1
M. Y. Lee S. H. Lee J. H. Park H. J. Han 《Cellular and molecular life sciences : CMLS》2009,66(8):1467-1478
Galectins have the potential to provide a promising alternative for unveiling the complexity of embryonic stem (ES) cell self-renewal,
although the mechanism by which galectins maintain ES cell self-renewal has yet to be identified. Galectin-1 increased [3H]-thymidine incorporation as well as cyclin expression and decreased p27kip1 expression. Src and caveolin-1 phosphorylation was increased by galectin-1, and phospho-caveolin-1 was inhibited by PP2.
In addition, inhibition of caveolin-1 by small interfering RNA and methyl-β-cyclodextrin (Mβ-CD) decreased galectin-1-induced
cyclin expression and [3H]-thymidine incorporation. Galectin-1 caused Akt and mTOR phosphorylation, which is involved in cyclin expression. Galectin-1-induced
phospho-Akt and -mTOR was inhibited by PP2, ERas siRNA, caveolin-1 siRNA and Mβ-CD. Furthermore, mTOR phosphorylation was
decreased by LY294002 and Akt inhibitor. Galectin-1-induced increase in cyclin expression and decrease in p27kip1 was blocked by Akt inhibitor and rapamycin. In conclusion, galectin-1 increased DNA synthesis in mouse ES cells via Src,
caveolin-1 Akt, and mTOR signaling pathways.
Received 30 October 2008; received after revision 18 February 2009; accepted 24 February 2009 相似文献
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S. Padilla U. C. Tran M. Jiménez-Hidalgo J. M. López-Martín A. Martín-Montalvo C. F. Clarke P. Navas C. Santos-Ocaña 《Cellular and molecular life sciences : CMLS》2009,66(1):173-186
Coenzyme Q is a lipid molecule required for respiration and antioxidant protection. Q biosynthesis in Saccharomyces cerevisiae requires nine proteins (Coq1p–Coq9p). We demonstrate in this study that Q levels are modulated during growth by its conversion
from demethoxy-Q (DMQ), a late intermediate. Similar conversion was produced when cells were subjected to oxidative stress
conditions. Changes in Q6/DMQ6 ratio were accompanied by changes in COQ7 gene mRNA levels encoding the protein responsible for the DMQ hydroxylation, the penultimate step in Q biosynthesis pathway.
Yeast coq null mutant failed to accumulate any Q late biosynthetic intermediate. However, in coq7 mutants the addition of exogenous Q produces the DMQ synthesis. Similar effect was produced by over-expressing ABC1/COQ8. These results support the existence of a biosynthetic complex that allows the DMQ6 accumulation and suggest that Coq7p is a control point for the Q biosynthesis regulation in yeast.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.
Received 04 September 2008; received after revision 22 October 2008; accepted 23 October 2008 相似文献
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Bile acids and bile alcohols in the form of their conjugates are amphipathic end products of cholesterol metabolism with multiple physiological functions. The great variety of bile acids and bile alcohols that are present in vertebrates are tabulated. Bile salts have an enterohepatic circulation resulting from efficient vectorial transport of bile salts through the hepatocyte and the ileal enterocyte; such transport leads to the accumulation of a pool of bile salts that cycles between the liver and intestine. Bile salt anions promote lipid absorption, enhance tryptic cleavage of dietary proteins, and have antimicrobial effects. Bile salts are signaling molecules, activating nuclear receptors in the hepatocyte and ileal enterocyte, as well as an increasing number of G-protein coupled receptors. Bile acids are used therapeutically to correct deficiency states, to decrease the cholesterol saturation of bile, or to decrease the cytotoxicity of retained bile acids in cholestatic liver disease. 相似文献
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Myosin I is a non-filamentous, single-headed, actin-binding motor protein and is present in a wide range of species from yeast to man. The role of these class I myosins have been studied extensively in simple eukaryotes, showing their role in diverse processes such as actin cytoskeleton organization, cell motility, and endocytosis. Recently, studies in metazoans have begun to reveal more specialized functions of myosin I. It will be a major challenge in the future to examine the physiological functions of each class I myosin in different cell types of metazoans. 相似文献
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E. Cohen-Hillel R. Mintz T. Meshel B.-Z. Garty A. Ben-Baruch 《Cellular and molecular life sciences : CMLS》2009,66(5):884-899
The chemokine CXCL8 is a powerful inducer of directional cell motility, primarily during inflammation. In this study, we found
that CXCL8 stimulation led to paxillin phosphorylation in normal neutrophils, and that both CXCL8 receptors (CXCR1 and CXCR2)
mediated CXCL8-induced paxillin phosphorylation. In CXCR2-transfected cells, the process depended on Gαi and Gαs coupling to CXCR2. Dominant negative (DN) paxillin increased CXCL8-induced adhesion and migration, indicating that endogenous
paxillin keeps migration at submaximal levels. Furthermore, using activating antibodies to β1 integrins, analyses with focal
adhesion kinase (FAK) DN variant (FRNK) and co-immunoprecipitations of FAK and paxillin, we found that β1 integrin ligation
cooperates with CXCL8-induced stimulation, leading to FAK activation and thereafter to FAK-mediated paxillin phosphorylation.
Our findings indicate that paxillin keeps directional motility at a restrained magnitude, and suggest that perturbations in
its activation may lead to chemotactic imbalance and to pathological conditions associated with excessive or reduced leukocyte
migration.
R. Mintz, T. Meshel: These authors contributed equally to this work.
Received 31 July 2008; received after revision 14 December 2008; accepted 16 December 2008 相似文献
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