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dc.contributor.authorYu, Xing
dc.contributor.authorScott, Stacy A
dc.contributor.authorPritchard, Rhys
dc.contributor.authorHouston, Todd A
dc.contributor.authorRalph, Stephen J
dc.contributor.authorBlanchard, Helen
dc.date.accessioned2017-11-27T04:21:11Z
dc.date.available2017-11-27T04:21:11Z
dc.date.issued2015
dc.identifier.issn0300-9084
dc.identifier.doi10.1016/j.biochi.2015.06.013
dc.identifier.urihttp://hdl.handle.net/10072/141489
dc.description.abstractIntracellular and extracellular functions of human galectin-1 are influenced by its redox surroundings due to the presence of six cysteines within its amino acid sequence. Galectin-1 recognises intracellular-membrane-anchored Ras proteins that act as molecular switches regulating multiple signal transduction pathways. Human tumours frequently express Ras proteins that have become continuously activated due to point mutations, and this typically leads to deregulation of tumour cell growth, angiogenesis and invasion of metastatic cancer cells. Of significance is that galectin-1 preferably recognises H-Ras, one of the human Ras isoforms, and in particular galectin-1 recognition of the H-Ras farnesyl moiety is paramount to H-Ras membrane anchorage, a prerequisite step for H-Ras-mediated signal transduction regulating normal cell growth and malignant transformation. Herein the impact of the redox state on galectin-1's ability to interact with farnesyl analogues is explored. We demonstrate for the first time that reduced galectin-1 directly binds farnesyl and does so in a carbohydrate-independent manner. A K28T mutation abolishes farnesyl recognition by reduced dimeric galectin-1 whilst its carbohydrate-binding activity is retained, thus demonstrating the presence of an independent region on galectin-1 pertaining to growth inhibitory activity. Intriguingly, oxidised galectin-1 also recognises farnesyl, the biological implication of this novel finding is yet to be elucidated. Further, the redox effect on galectin-1 extracellular function was investigated and we discover that oxidised galectin-1 demonstrates a protective effect upon acute lymphoblastic leukaemia cells challenged by oxidative stress.
dc.description.peerreviewedYes
dc.languageEnglish
dc.language.isoeng
dc.publisherElsevier
dc.relation.ispartofpagefrom8
dc.relation.ispartofpageto16
dc.relation.ispartofjournalBiochimie
dc.relation.ispartofvolume116
dc.subject.fieldofresearchBiochemistry and Cell Biology not elsewhere classified
dc.subject.fieldofresearchBiochemistry and Cell Biology
dc.subject.fieldofresearchcode060199
dc.subject.fieldofresearchcode0601
dc.titleRedox state influence on human galectin-1 function
dc.typeJournal article
dc.type.descriptionC1 - Articles
dc.type.codeC - Journal Articles
gro.facultyOffice of the Snr Dep Vice Chancellor, Institute for Glycomics
gro.hasfulltextNo Full Text
gro.griffith.authorHouston, Todd A.
gro.griffith.authorRalph, Stephen J.
gro.griffith.authorBlanchard, Helen
gro.griffith.authorScott, Stacy
gro.griffith.authorYu, Xing
gro.griffith.authorPritchard, Rhys


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