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Galectin

About: Galectin is a research topic. Over the lifetime, 2076 publications have been published within this topic receiving 103409 citations. The topic is also known as: IPR001079 & Galectin.


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Journal ArticleDOI
TL;DR: It is concluded that the β-galactoside binding site represents the primary targeting motif of galectins defining a galectin export machinery that makes use of β-Galactosid–containing surface molecules as export receptors for intracellular galECTin-1.
Abstract: Galectin-1 is a component of the extracellular matrix as well as a ligand of cell surface counter receptors such as beta-galactoside-containing glycolipids, however, the molecular mechanism of galectin-1 secretion has remained elusive. Based on a nonbiased screen for galectin-1 export mutants we have identified 26 single amino acid changes that cause a defect of both export and binding to counter receptors. When wild-type galectin-1 was analyzed in CHO clone 13 cells, a mutant cell line incapable of expressing functional galectin-1 counter receptors, secretion was blocked. Intriguingly, we also find that a distant relative of galectin-1, the fungal lectin CGL-2, is a substrate for nonclassical export from Chinese hamster ovary (CHO) cells. Alike mammalian galectin-1, a CGL-2 mutant defective in beta-galactoside binding, does not get exported from CHO cells. We conclude that the beta-galactoside binding site represents the primary targeting motif of galectins defining a galectin export machinery that makes use of beta-galactoside-containing surface molecules as export receptors for intracellular galectin-1.

120 citations

Journal ArticleDOI
TL;DR: It is shown that the p16INK4a‐dependent impact on growth‐regulatory lectins is not limited to galectin‐1, but also concerns galECTin‐3.
Abstract: The tumor suppressor p16INK4a has functions beyond cell-cycle control via cyclin-dependent kinases. A coordinated remodeling of N- and O-glycosylation, and an increase in the presentation of the endogenous lectin galectin-1 sensing these changes on the surface of p16INK4a-expressing pancreatic carcinoma cells (Capan-1), lead to potent pro-anoikis signals. We show that the p16INK4a-dependent impact on growth-regulatory lectins is not limited to galectin-1, but also concerns galectin-3. By monitoring its expression in relation to p16INK4a status, as well as running anoikis assays with galectin-3 and cell transfectants with up- or downregulated lectin expression, a negative correlation between anoikis and the presence of this lectin was established. Nuclear run-off and northern blotting experiments revealed an effect of the presence of p16INK4a on steady-state levels of galectin-3-specific mRNA that differed from decreasing the transcriptional rate. On the cell surface, galectin-3 interferes with galectin-1, which initiates signaling toward its pro-anoikis activity via caspase-8 activation. The detected opposite effects of p16INK4a at the levels of growth-regulatory galectins-1 and -3 shift the status markedly towards the galectin-1-dependent pro-anoikis activity. A previously undescribed orchestrated fine-tuning of this effector system by a tumor suppressor is discovered.

120 citations

Journal ArticleDOI
TL;DR: The fundamental parameters responsible for selectivity by the fungal representative, CGL2, are dissected to reveal that this prototype galectin achieves increased substrate specificity by accommodating substituted oligosaccharides of the mammalian blood group A/B type in an extended binding cleft.

120 citations

Journal ArticleDOI
TL;DR: X‐ray structural analysis of selected compounds in complex with galectin‐3 revealed that both the aryltriazolyl moieties and fluoro substituents on the compounds are involved in key interactions responsible for exceptional affinities towards galectins‐1 and ‐3.
Abstract: Discovery of glycan-competitive galectin-3-binding compounds that attenuate lung fibrosis in a murine model and that block intracellular galectin-3 accumulation at damaged vesicles, hence revealing galectin-3-glycan interactions involved in fibrosis progression and in intracellular galectin-3 activities, is reported. 3,3'-Bis-(4-aryltriazol-1-yl)thiodigalactosides were synthesized and evaluated as antagonists of galectin-1, -2, -3, and -4 N-terminal, -4 C-terminal, -7 and -8 N-terminal, -9 N-terminal, and -9 C-terminal domains. Compounds displaying low-nanomolar affinities for galectins-1 and -3 were identified in a competitive fluorescence anisotropy assay. X-ray structural analysis of selected compounds in complex with galectin-3, together with galectin-3 mutant binding experiments, revealed that both the aryltriazolyl moieties and fluoro substituents on the compounds are involved in key interactions responsible for exceptional affinities towards galectin-3. The most potent galectin-3 antagonist was demonstrated to act in an assay monitoring galectin-3 accumulation upon amitriptyline-induced vesicle damage, visualizing a biochemically/medically relevant intracellular lectin-carbohydrate binding event and that it can be blocked by a small molecule. The same antagonist administered intratracheally attenuated bleomycin-induced pulmonary fibrosis in a mouse model with a dose/response profile comparing favorably with that of oral administration of the marketed antifibrotic compound pirfenidone.

120 citations


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Performance
Metrics
No. of papers in the topic in previous years
YearPapers
2023182
2022176
2021107
2020120
201995
2018119