ABC-ATPases, adaptable energy generators fuelling transmembrane movement of a variety of molecules in organisms from bacteria to humans

Holland, I. B.; Blight, Mark A.

doi:10.1006/jmbi.1999.2993

Cited by 529 publications

(446 citation statements)

References 110 publications

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“…Walker motifs are found in a broad range of ATPases, and thereby provide predictive value for ATPases (31). Through detailed examination of human endostatin sequence, we found that endostatin comprises a Walker A motif variant (GXXGXXK; ref.…”

Section: Endostatin Has Novel Atpase Activitymentioning

confidence: 99%

Endostatin Has ATPase Activity, Which Mediates Its Antiangiogenic and Antitumor Activities

Wang

Liu

et al. 2015

Molecular Cancer Therapeutics

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Endostatin is an endogenous angiogenesis inhibitor with broad-spectrum antitumor activities. Although the molecular mechanisms of endostatin have been extensively explored, the intrinsic biochemical characteristics of endostatin are not completely understood. Here, we revealed for the first time that endostatin embedded novel ATPase activity. Moreover, mutagenesis study showed that the ATPase activity of endostatin mutants positively correlated with effects on endothelial cell activities and tumor growth. E-M, an endostatin mutant with higher ATPase activity than that of wild-type (WT) endostatin, significantly increased endostatin-mediated inhibitory effects on endothelial cell proliferation, migration, tube formation, and adhesion. In vivo study showed that E-M displayed enhanced antitumor effects compared with WT. On the other hand, K96A, K96R, and E176A, endostatin mutants with lower ATPase activities than that of WT, showed reduced or comparable effects on targeting both in vitro endothelial cell activities and in vivo tumor angiogenesis and tumor growth. Furthermore, endostatin and its mutants exhibited distinct abilities in regulations of gene expression (Id1, Id3), cell signaling (Erk, p38, and Src phosphorylation), and intracellular ATP levels. Collectively, our study demonstrates that endostatin has novel ATPase activity, which mediates its antiangiogenic and antitumor activities, suggesting that construction of endostatin analogues with high ATPase activity may provide a new direction for the development of more potent antiangiogenic drugs.

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Section: Endostatin Has Novel Atpase Activitymentioning

confidence: 99%

Endostatin Has ATPase Activity, Which Mediates Its Antiangiogenic and Antitumor Activities

Wang

Liu

et al. 2015

Molecular Cancer Therapeutics

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“…ATP-binding cassette (ABC) transporters are an important class of transport proteins, which are widely distributed in all domains of life and are involved in varying processes such as substrate uptake or export, osmosensing and osmoregulation, and antigen processing (Holland and Blight, 1999). In humans, mutations in ABC transporter often result in severe diseases such as cystic fibrosis, adrenoleukodystrophy, while ABC transporters are also associated with multidrug resistance of tumor cells.…”

Section: Introductionmentioning

confidence: 99%

Insights into ABC Transport in Archaea

Albers

Koning

Konings

et al. 2004

J Bioenerg Biomembr

101

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In archaea, ATP-binding cassette (ABC) transporters play a crucial role in substrate uptake, export, and osmoregulation. Archaeal substrate-binding-protein-dependent ABC transporters are equipped with a very high affinity for their cognate substrates which provide these organisms with the ability to efficiently scavenge substrates from their environment even when present only at low concentration. Further adaptations to the archaeal way of life are especially found in the domain organization and anchoring of the substrate-binding proteins to the membrane. Examination of the signal peptides of binding proteins of 14 archaeal genomes showed clear differences between euryarchaeotes and crenarchaeotes. Furthermore, a profiling and comparison of ABC transporters in the three sequenced pyrococcal strains was performed.

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“…P-glycoprotein is a member of the ABC superfamily of transporters (Holland and Blight, 1999) and is able to confer resistance by actively extruding an extraordinarily diverse range of chemotherapeutic agents and a significant amount of research effort has been directed towards understanding and circumventing the actions of P-gp in vivo. But has the contribution of P-gp to drug resistance warranted this attention?…”

mentioning

confidence: 99%

The expression of P-glycoprotein does influence the distribution of novel fluorescent compounds in solid tumour models

et al. 2003

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Solid tumours display a complex drug resistance phenotype that involves inherent and acquired mechanisms. Multicellular resistance is an inherent feature of solid tumours and is known to present significant barriers to drug permeation in tumours. Given this barrier, do acquired resistance mechanisms such as P-glycoprotein (P-gp) contribute significantly to resistance? To address this question, the multicellular tumour spheroid (MCTS) model was used to examine the influence of P-gp on drug distribution in solid tissue. Tumour spheroids (TS) were generated from either drug-sensitive MCF7 WT cells or a drug-resistant, P-gp-expressing derivative MCF7 Adr . Confocal microscopy was used to measure time courses and distribution patterns of three fluorescent compounds; calcein-AM, rhodamine123 and BODIPY-taxol. These compounds were chosen because they are all substrates for P-gp-mediated transport, exhibit high fluorescence and are chemically dissimilar. For example, BODIPY-taxol and rhodamine 123 showed high accumulation and distributed extensively throughout the TS WT , whereas calcein-AM accumulation was restricted to the outermost layers. The presence of P-gp in TS Adr resulted in negligible accumulation, regardless of the compound. Moreover, the inhibition of P-gp by nicardipine restored intracellular accumulation and distribution patterns to levels observed in TS WT . The results demonstrate the effectiveness of P-gp in modulating drug distribution in solid tumour models. However, the penetration of agents throughout the tissue is strongly determined by the physico-chemical properties of the individual compounds.

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ABC-ATPases, adaptable energy generators fuelling transmembrane movement of a variety of molecules in organisms from bacteria to humans

Cited by 529 publications

References 110 publications

Endostatin Has ATPase Activity, Which Mediates Its Antiangiogenic and Antitumor Activities

Endostatin Has ATPase Activity, Which Mediates Its Antiangiogenic and Antitumor Activities

Insights into ABC Transport in Archaea

The expression of P-glycoprotein does influence the distribution of novel fluorescent compounds in solid tumour models

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