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51.
52.
It has become evident that caspases function in nonapoptotic cellular processes in addition to the canonical role for caspases in apoptotic cell death. We recently demonstrated that the Drosophila effector caspase Dcp-1 localizes to the mitochondria and positively regulates starvation-induced autophagic flux during mid-oogenesis. Loss of Dcp-1 leads to elongation of the mitochondrial network, increased levels of the adenine nucleotide translocase sesB, increased ATP levels, and a reduction in autophagy. We found that sesB is a negative regulator of autophagic flux, and Dcp-1 interacts with sesB in a nonproteolytic manner to regulate its stability, uncovering a novel mechanism of mitochondrial associated, caspase-mediated regulation of autophagy in vivo. 相似文献
53.
Mikhail F AlexeyevHerbert H Winkler 《生物化学与生物物理学报:生物膜》2002,1565(1):136-142
The ATP/ADP translocase (Tlc) of Rickettsia prowazekii is a basic protein with isoelectric point (pI)=9.84. It is conceivable, therefore, that basic residues in this protein are involved in electrostatic interactions with negatively charged substrates. We tested this hypothesis by individually mutating all basic residues in Tlc to Cys. Unexpectedly, mutations of only 20 out of 51 basic residues resulted in greater than 80% inhibition of transport activity. Moreover, 12 of 51Cys-substitution mutants exhibited higher than wild-type (WT) activity. At least in one case this up-effect was additive and the double mutant Lys422Cys Lys427Cys transported ATP five-fold better than WT protein. Since in these two single mutants and in the corresponding double mutant Km's were similar to that of WT protein, we conclude that Tlc may have evolved a mechanism that limits the transporter's exchange rate and that at least these two basic residues play a key role in that mechanism.Based on the alignment of 16 Tlc homologs, the loss of activity in the mutants poorly correlates with charge conservation within the Tlc family. Also, despite the presence of three positively charged and one negatively charged intramembrane residues, we have failed to identify potential charge pairs (salt bridges) by either charge reversal or charge neutralization approaches. 相似文献
54.
R. J. Phillips D. C. Hickleton P. E. Boehmer P. T. Emmerson 《Molecular & general genetics : MGG》1997,254(3):319-329
To investigate the role that the individual subunits play in the ATP-dependent helicase activity of the RecBCD protein we
have investigated the ability of the RecB, RecC and RecD proteins to displace various 20-mer oligonucleotides annealed to
either end or to the centre of an oligonucleotide 60 bases long. The results show that the only subunit which can displace
the 20-mers in the absence of the other subunits is the RecB protein. Moreover, the 20-mer is displaced only if it is annealed
to the 60-mer at the 5′ end or the middle, suggesting that the RecB protein translocates along the 60-mer in the 3′ to 5′
direction, displacing annealed 20-mers as it proceeds. We have shown that reconstituted RecBC and RecBCD complexes displace
the 20-mers but, unlike RecB, they do not require a 3′-ended single-stranded region for helicase action, but can displace
the 20-mers from either end of the 60-mer. The level of helicase activity of the RecBC complex is considerably greater than
that of RecB alone, and the activity of the RecBCD complex appears to be greater still. This hierarchy of activity is also
shown by DNA binding studies, but is not reflected in the ATPase activities of the enzymes. We have also shown that the ability
of trypsin to cleave various sites on the RecB molecule is modified by the presence of ATP or ATP-γ-S, suggesting that conformational
changes may be induced in RecB upon ATP binding. We discuss a model for the ATP-driven, unidirectional motion of the RecB
translocase along single-stranded DNA. In this model, the RecB molecule binds to single-stranded DNA and then translocates
along it, one base at a time, in the 3′ to 5′ direction, by a `ratchet' mechanism in which repeated stretching and contraction
of the protein is coupled to ATP hydrolysis. The RecC protein in the RecBC complex is proposed to act as a `sliding clamp'
which increases processivity by preventing dissociation.
Received: 10 September 1996 / Accepted: 18 November 1996 相似文献
55.
AtRAD5A is a DNA translocase harboring a HIRAN domain which confers binding to branched DNA structures and is required for DNA repair in vivo 下载免费PDF全文
Daniela Kobbe Andy Kahles Maria Walter Tobias Klemm Anja Mannuss Alexander Knoll Manfred Focke Holger Puchta 《The Plant journal : for cell and molecular biology》2016,88(4):521-530
DNA lesions such as crosslinks represent obstacles for the replication machinery. Nonetheless, replication can proceed via the DNA damage tolerance pathway also known as postreplicative repair pathway. SNF2 ATPase Rad5 homologs, such as RAD5A of the model plant Arabidopsis thaliana, are important for the error‐free mode of this pathway. We able to demonstrate before, that RAD5A is a key factor in the repair of DNA crosslinks in Arabidopsis. Here, we show by in vitro analysis that AtRAD5A protein is a DNA translocase able to catalyse fork regression. Interestingly, replication forks with a gap in the leading strand are processed best, in line with its suggested function. Furthermore AtRAD5A catalyses branch migration of a Holliday junction and is furthermore not impaired by the DNA binding of a model protein, which is indicative of its ability to displace other proteins. Rad5 homologs possess HIRAN (Hip116, Rad5; N‐terminal) domains. By biochemical analysis we were able to demonstrate that the HIRAN domain variant from Arabidopsis RAD5A mediates structure selective DNA binding without the necessity for a free 3′OH group as has been shown to be required for binding of HIRAN domains in a mammalian RAD5 homolog. The biological importance of the HIRAN domain in AtRAD5A is demonstrated by our result that it is required for its function in DNA crosslink repair in vivo. 相似文献
56.
Estelle Crozat Adrien Meglio Jean‐François Allemand Claire E Chivers Mark Howarth Catherine Vénien‐Bryan David J Sherratt 《The EMBO journal》2010,29(8):1423-1433
FtsK translocates dsDNA directionally at >5 kb/s, even under strong forces. In vivo, the action of FtsK at the bacterial division septum is required to complete the final stages of chromosome unlinking and segregation. Despite the availability of translocase structures, the mechanism by which ATP hydrolysis is coupled to DNA translocation is not understood. Here, we use covalently linked translocase subunits to gain insight into the DNA translocation mechanism. Covalent trimers of wild‐type subunits dimerized efficiently to form hexamers with high translocation activity and an ability to activate XerCD‐dif chromosome unlinking. Covalent trimers with a catalytic mutation in the central subunit formed hexamers with two mutated subunits that had robust ATPase activity. They showed wild‐type translocation velocity in single‐molecule experiments, activated translocation‐dependent chromosome unlinking, but had an impaired ability to displace either a triplex oligonucleotide, or streptavidin linked to biotin‐DNA, during translocation along DNA. This separation of translocation velocity and ability to displace roadblocks is more consistent with a sequential escort mechanism than stochastic, hand‐off, or concerted mechanisms. 相似文献
57.
Matthew J Harris Irwin M Arias 《Biochimica et Biophysica Acta (BBA)/Molecular and Cell Biology of Lipids》2003,1633(2):127-131
ATP8B1/FIC1 is a member of the Type IV P-type ATPase family, which function as ATP dependent aminophospholipid translocases (APLT). We identified two familial intrahepatic cholestasis type 1 (FIC1) homologues, ATP8B2 and ATP8B3, with 53% and 45% amino acid identity, respectively. The expression profile for each gene was determined using a 73-tissue human RNA expression array. The subfamily of FIC1-like proteins is expressed in a wide range of tissues. Given that mutations in FIC1 result in liver disease, these proteins may have important roles in other organs in which they are candidates for genetic and acquired diseases. 相似文献
58.
Cationic liposomes are used as efficient carriers for gene delivery into mammalian cells due to their ability to bind nucleic acids, adsorb onto the cell surface and fuse with negatively charged membranes. This last property enables the release and escape of their cargo from endosomal compartments. The efficiency of this fusion mainly depends on the surface charge of the target membranes. Here, we report that cells of two different lines, epithelial adenocarcinoma HeLa and lymphocytic leukemia Jurkat T, which externalize PS, are more susceptible to fusion with DOTAP liposomes than control cells. We compared the ability to undergo fusion of untreated and apoptotic cells. Apoptosis was induced by various pro-apoptotic agents and treatments, namely: incubation in the presence of MnCl(2), cytostatic drugs fludarabine and mitoxantrone, staurosporine and serum depletion in the case of HeLa cells. Jurkat T cells were treated similarly except apoptosis was additionally induced by incubation in the presence of 4% EtOH. Epithelial cells fused with the highest efficiencies of lipid mixing, when pretreated with staurosporine. Jurkat T cells were less susceptible to fusion, but they also displayed an increase in fusion efficiency after the induction of apoptosis. Alternatively, we treated the cells with metabolic inhibitors causing ATP-depletion in order to inactivate aminophospholipid translocase. After ATP-depletion, HeLa and Jurkat T cells fused with DOTAP liposomes with higher efficiencies than control cells. Our conclusion is that the lipid asymmetry of natural membranes may limit fusion with cationic liposomes. 相似文献
59.
G6P translocase (G6PT) is thought to play a crucial role in transducing intracellular signaling events in brain tumor-derived cancer cells. In this report, we investigated the contribution of G6PT to the control of U-87 brain tumor-derived glioma cell survival using small interfering RNA (siRNA)-mediated suppression of G6PT. Three siRNA constructs were generated and found to suppress up to 91% G6PT gene expression. Flow cytometry analysis of propidium iodide/annexin-V-stained cells indicated that silencing the G6PT gene induced necrosis and late apoptosis. The anticancer agent curcumin, also inhibited G6PT gene expression by more than 90% and triggered U-87 glioma cells death. Overexpression of recombinant G6PT rescued the cells from curcumin-induced cell death. Targeting G6PT expression may provide a new mechanistic rationale for the action of chemopreventive drugs and lead to the development of new anti-cancer strategies. 相似文献
60.
Brinkmann JF Pelsers MM van Nieuwenhoven FA Tandon NN van der Vusse GJ Glatz JF 《Molecular and cellular biochemistry》2006,284(1-2):127-134
Evidence is accumulating that the heavily glycosylated integral membrane protein fatty acid translocase (FAT/CD36) is involved
in the transport of long-chain fatty acids across the sarcolemma of heart muscle cells. The aim of this study was to analyse
the distribution between FAT/CD36 present in cardiac myocytes and endothelial cells. We therefore developed a method to purify
FAT/CD36 from total rat heart and isolated cardiomyocytes, and used the proteins as standards in an immunochemical assay.
Two steps, chromatography on wheat germ agglutinin-agarose and anion-exchange chromatography on Q-Sepharose fast flow, were
sufficient for obtaining the protein in a > 95% pure form. When used to isolate FAT/CD36 from total heart tissue, the FAT/CD36
yield of the method was 9% and the purification factor was 64. Purifying FAT/CD36 from isolated cardiomyocytes yielded the
same 88 kDa protein band on SDS-PAGE gels and reactivity of this band on western blots was comparable to that of the FAT/CD36
isolated from total hearts. Quantifying FAT/CD36 contents by western blotting showed that the amounts of FAT/CD36 that are
present in isolated cardiomyocytes (10 ± 3 μg/mg protein) and total hearts (14 ± 4 μg/mg protein) are of comparable magnitude.
Immunofluorescence labelling showed that at least a part of the FAT/CD36 present in the cardiomyocyte is associated with the
sarcolemma. This study established that FAT/CD36 is a relatively abundant protein in the cardiomyocyte. In addition, the further
developed purification procedure is the first method for isolating FAT/CD36 from rat heart and cardiomyocyte FAT/CD36. 相似文献