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排序方式: 共有10000条查询结果,搜索用时 46 毫秒
931.
G. M. C. Janssen P. Schwertman T. A. T. Wanga R. S. Jahangir Tafrechi P. J. A. van den Broek A. K. Raap 《Cellular and molecular life sciences : CMLS》2009,66(4):721-730
Cytoplasmic translation is under sophisticated control but how cells adapt its rate to constitutive loss of mitochondrial
oxidative phosphorylation is unknown. Here we show that translation is repressed in cells with the pathogenic A3243G mtDNA
mutation or in mtDNA-less ρ0 cells by at least two distinct pathways, one transiently targeting elongation factor eEF-2 and the other initiation factor
eIF-2α constitutively. Under conditions of exponential cell growth and mammalian target of rapamycin (mTOR) activation, eEF-2
becomes transiently phosphorylated by an AMP-activated protein kinase (AMPK)-dependent pathway, especially high in mutant
cells. Independent of AMPK and mTOR, eIF-2α is constitutively phosphorylated in mutant cells, likely a signature of endoplasmic
reticulum (ER)-stress response induced by the loss of oxidative phosphorylation. While the AMPK/eEF-2K/eEF-2 pathway appears
to function in adaptation to physiological fluctuations in ATP levels in the mutant cells, the ER stress signified by constitutive
protein synthesis inhibition through eIF-2α-mediated repression of translation initiation may have pathobiochemical consequences.
Received 29 October 2008; received after revision 11 December 2008; accepted 16 December 2008 相似文献
932.
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
933.
A. Beqqali W. van Eldik C. Mummery R. Passier 《Cellular and molecular life sciences : CMLS》2009,66(5):800-813
Studies on identification, derivation and characterization of human stem cells in the last decade have led to high expectations
in the field of regenerative medicine. Although it is clear that for successful stem cell-based therapy several obstacles
have to be overcome, other opportunities lay ahead for the use of human stem cells. A more immediate application would be
the development of human models for cell-type specific differentiation and disease in vitro. Cardiomyocytes can be generated from stem cells, which have been shown to follow similar molecular events of cardiac development
in vivo. Furthermore, several monogenic cardiovascular diseases have been described, for which in vitro models in stem cells could be generated. Here, we will discuss the potential of human embryonic stem cells, cardiac stem
cells and the recently described induced pluripotent stem cells as models for cardiac differentiation and disease.
Received 07 August 2008; received after revision 26 September 2008; accepted 03 October 2008 相似文献
934.
R. P. Massengo-Tiassé J. E. Cronan 《Cellular and molecular life sciences : CMLS》2009,66(9):1507-1517
The enoyl-acyl carrier protein reductase (ENR) is the last enzyme in the fatty acid elongation cycle. Unlike most enzymes
in this essential pathway, ENR displays an unusual diversity among organisms. The growing interest in ENRs is mainly due to
the fact that a variety of both synthetic and natural antibacterial compounds are shown to specifically target their activity.
The primary anti-tuberculosis drug, isoniazid, and the broadly used antibacterial compound, triclosan, both target this enzyme.
In this review, we discuss the diversity of ENRs, and their inhibitors in the light of current research progress.
Received 3 November 2008; received after revision 5 December 2008; accepted 8 December 2008 相似文献
935.
Functions and pathologies of BiP and its interaction partners 总被引:1,自引:1,他引:0
J. Dudek J. Benedix S. Cappel M. Greiner C. Jalal L. Müller R. Zimmermann 《Cellular and molecular life sciences : CMLS》2009,66(9):1556-1569
The endoplasmic reticulum (ER) is involved in a variety of essential and interconnected processes in human cells, including
protein biogenesis, signal transduction, and calcium homeostasis. The central player in all these processes is the ER-lumenal
polypeptide chain binding protein BiP that acts as a molecular chaperone. BiP belongs to the heat shock protein 70 (Hsp70)
family and crucially depends on a number of interaction partners, including co-chaperones, nucleotide exchange factors, and
signaling molecules. In the course of the last five years, several diseases have been linked to BiP and its interaction partners,
such as a group of infectious diseases that are caused by Shigella toxin producing E. coli. Furthermore, the inherited diseases Marinesco-Sj?gren syndrome, autosomal dominant polycystic liver disease, Wolcott-Rallison
syndrome, and several cancer types can be considered BiP-related diseases. This review summarizes the physiological and pathophysiological
characteristics of BiP and its interaction partners.
Received 20 November 2008; received after revision 09 December 2008; accepted 12 December 2008 相似文献
936.
A. Shukla P. Chaurasia S. R. Bhaumik 《Cellular and molecular life sciences : CMLS》2009,66(8):1419-1433
Methylation of lysine residues of histones is associated with functionally distinct regions of chromatin, and, therefore,
is an important epigenetic mark. Over the past few years, several enzymes that catalyze this covalent modification on different
lysine residues of histones have been discovered. Intriguingly, histone lysine methylation has also been shown to be cross-regulated
by histone ubiquitination or the enzymes that catalyze this modification. These covalent modifications and their cross-talks
play important roles in regulation of gene expression, heterochromatin formation, genome stability, and cancer. Thus, there
has been a very rapid progress within past several years towards elucidating the molecular basis of histone lysine methylation
and ubiquitination, and their aberrations in human diseases. Here, we discuss these covalent modifications with their cross-regulation
and roles in controlling gene expression and stability.
Received 24 September 2008; received after revision 21 November 2008; accepted 28 November 2008 相似文献
937.
Dirk M. Walther Doron Rapaport Jan Tommassen 《Cellular and molecular life sciences : CMLS》2009,66(17):2789-2804
Membrane-embedded β-barrel proteins span the membrane via multiple amphipathic β-strands arranged in a cylindrical shape.
These proteins are found in the outer membranes of Gram-negative bacteria, mitochondria and chloroplasts. This situation is
thought to reflect the evolutionary origin of mitochondria and chloroplasts from Gram-negative bacterial endosymbionts. β-barrel
proteins fulfil a variety of functions; among them are pore-forming proteins that allow the flux of metabolites across the
membrane by passive diffusion, active transporters of siderophores, enzymes, structural proteins, and proteins that mediate
protein translocation across or insertion into membranes. The biogenesis process of these proteins combines evolutionary conservation
of the central elements with some noticeable differences in signals and machineries. This review summarizes our current knowledge
of the functions and biogenesis of this special family of proteins. 相似文献
938.
Berger W Steiner E Grusch M Elbling L Micksche M 《Cellular and molecular life sciences : CMLS》2009,66(1):43-61
The unique and evolutionary highly conserved major vault protein (MVP) is the main component of ubiquitous, large cellular
ribonucleoparticles termed vaults. The 100 kDa MVP represents more than 70% of the vault mass which contains two additional
proteins, the vault poly (ADP-ribose) polymerase (vPARP) and the telomerase-associated protein 1 (TEP1), as well as several
short untranslated RNAs (vRNA). Vaults are almost ubiquitously expressed and, besides chemotherapy resistance, have been implicated
in the regulation of several cellular processes including transport mechanisms, signal transmissions and immune responses.
Despite a growing amount of data from diverse species and systems, the definition of precise vault functions is still highly
complex and challenging. Here we review the current knowledge on MVP and vaults with focus on regulatory functions in intracellular
signal transduction and immune defence.
Received 27 June 2008; received after revision 25 July 2008; accepted 30 July 2008 相似文献
939.
This paper evaluates the performance of conditional variance models using high‐frequency data of the National Stock Index (S&P CNX NIFTY) and attempts to determine the optimal sampling frequency for the best daily volatility forecast. A linear combination of the realized volatilities calculated at two different frequencies is used as benchmark to evaluate the volatility forecasting ability of the conditional variance models (GARCH (1, 1)) at different sampling frequencies. From the analysis, it is found that sampling at 30 minutes gives the best forecast for daily volatility. The forecasting ability of these models is deteriorated, however, by the non‐normal property of mean adjusted returns, which is an assumption in conditional variance models. Nevertheless, the optimum frequency remained the same even in the case of different models (EGARCH and PARCH) and different error distribution (generalized error distribution, GED) where the error is reduced to a certain extent by incorporating the asymmetric effect on volatility. Our analysis also suggests that GARCH models with GED innovations or EGRACH and PARCH models would give better estimates of volatility with lower forecast error estimates. Copyright © 2008 John Wiley & Sons, Ltd. 相似文献
940.
Jonathan M. Weinberg 《Studies in history and philosophy of science》2009,40(2):227-232
Experimental philosophy is often regarded as a category mistake. Even those who reject that view typically see it as irrelevant to standard philosophical projects. We argue that neither of these claims can be sustained and illustrate our view with a sketch of the rich interconnections with philosophy of science. 相似文献