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81.
82.
Edlich F Weiwad M Erdmann F Fanghänel J Jarczowski F Rahfeld JU Fischer G 《The EMBO journal》2005,24(14):2688-2699
FKBP-type peptidyl prolyl cis/trans isomerases (PPIases) are folding helper enzymes involved in the control of functional regrowth of damaged sciatic, cortical cholinergic, dopaminergic and 5-HT neurones. Here, we show that the constitutively inactive human FK506-binding protein 38 (FKBP38) is capable of responding directly to intracellular Ca2+ rise through formation of a heterodimeric Ca2+/calmodulin/FKBP38 complex. Only complex formation creates an enzymatically active FKBP, displaying affinity for Bcl-2 mediated through the PPIase site. Association between Bcl-2 and the active site of Ca2+/calmodulin/FKBP38 regulates Bcl-2 function and thereby participates in the promotion of apoptosis in neuronal tissues. FKBP38 proapoptotic function mediated by this interaction is abolished by either potent inhibitors of the PPIase activity of the Ca2+/calmodulin/FKBP38 complex or RNA interference-mediated depletion of FKBP38, promoting neuronal cell survival. 相似文献
83.
Schneider G 《Current opinion in structural biology》2005,15(6):629-636
Aromatic polyketides are secondary metabolites that afford some of the most common antibiotics and anti-cancer drugs currently in clinical use. Not least because of their medical importance, the biosynthesis of these compounds has attracted considerable interest during the past few years; important advances have been made in the structural and mechanistic characterisation of the enzymes involved. These studies are expected to have implications for the production of novel therapeutic agents by combinatorial biosynthesis. 相似文献
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The assembly of spliceosomal U-rich small nuclear ribonucleoproteins (U snRNPs) is an ATP-dependent process mediated by the coordinated action of the SMN and the PRMT5 complex. Here, we provide evidence that the activity of this assembly machinery is regulated by means of post-translational modification. We show that two main components of the SMN/PRMT5 system, namely the survival motor neuron (SMN) protein (reduced levels thereof causing spinal muscular atrophy) and pICln, are phosphorylated in vivo. Both proteins share a previously unknown motif containing either one or two phosphoserines. Alteration of these residues in SMN (serines 28 and 31) significantly impairs the activity of the SMN complex. Despite the presence of SMN in both the nucleus and cytoplasm, we find that only the latter promotes efficient SMN-mediated U snRNP assembly activity. As cytoplasmic SMN is phosphorylated to a much larger extent, we hypothesize that this modification is a key activator of the SMN complex. 相似文献
86.
Liliane?VenturaEmail author Gabriel?Torres?de Jesus Gunter?Camilo Dablas?de Oliveira Sidney?JF?Sousa 《Biomedical engineering online》2005,4(1):70
Background
The authors have developed a small portable device for the objective measurement of the transparency of corneas stored in preservative medium, for use by eye banks in evaluation prior to transplantation. 相似文献87.
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Malatesta M Scassellati C Meister G Plöttner O Bühler D Sowa G Martin TE Keidel E Fischer U Fakan S 《Experimental cell research》2004,292(2):312-321
Mutations in the survival of motor neuron (SMN) gene are the major cause of spinal muscular atrophy (SMA). The SMN gene encodes a 38-kDa protein that localises in the cytoplasm and in nuclear bodies termed Gemini of coiled bodies (gems). When visualised by immunofluorescence microscopy, gems often appeared either in close proximity to, or entirely overlapping with coiled (Cajal) bodies (CBs) implying a possible functional relationship between these nuclear domains. With the aim of identifying subnuclear compartments corresponding to gems, we have investigated the intranuclear localisation of SMN and of its interacting protein Gemin2 by immunoelectron microscopy in cultured cells and in liver cells of hibernating dormouse. These antigens are highly enriched in round-shaped electron-dense fibro-granular clusters (EFGCs), which also display a biochemical composition similar to gems visualised by immunofluorescence microscopy. Our data reveal a novel SMN/Gemin2 containing nuclear domain and support the idea that it represents the structural counterpart of gems seen in the light microscope. 相似文献
90.
Calcium and mitochondria 总被引:8,自引:0,他引:8
The literature suggests that the physiological functions for which mitochondria sequester Ca(2+) are (1). to stimulate and control the rate of oxidative phosphorylation, (2). to induce the mitochondrial permeability transition (MPT) and perhaps apoptotic cell death, and (3). to modify the shape of cytosolic Ca(2+) pulses or transients. There is strong evidence that intramitochondrial Ca(2+) controls both the rate of ATP production by oxidative phosphorylation and induction of the MPT. Since the results of these processes are so divergent, the signals inducing them must not be ambiguous. Furthermore, as pointed out by Balaban [J. Mol. Cell. Cardiol. 34 (2002 ) 11259-11271], for any repetitive physiological process dependent on intramitochondrial free Ca(2+) concentration ([Ca(2+)](m)), a kind of intramitochondrial homeostasis must exist so that Ca(2+) influx during the pulse is matched by Ca(2+) efflux during the period between pulses to avoid either Ca(2+) buildup or depletion. In addition, mitochondrial Ca(2+) transport modifies both spatial and temporal aspects of cytosolic Ca(2+) signaling. Here, we look at the amounts of Ca(2+) necessary to mediate the functions of mitochondrial Ca(2+) transport and at the mechanisms of transport themselves in order to set up a hypothesis about how the mechanisms carry out their roles. The emphasis here is on isolated mitochondria and on general mitochondrial properties in order to focus on how mitochondria alone may function to fulfill their physiological roles even though the interactions of mitochondria with other organelles, particularly with endoplasmic and sarcoplasmic reticulum [Sci. STKE re1 (2004) 1-9], may also influence this story. 相似文献