| pubmed-article:12642862 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:12642862 | lifeskim:mentions | umls-concept:C0086418 | lld:lifeskim |
| pubmed-article:12642862 | lifeskim:mentions | umls-concept:C0007634 | lld:lifeskim |
| pubmed-article:12642862 | lifeskim:mentions | umls-concept:C0035820 | lld:lifeskim |
| pubmed-article:12642862 | lifeskim:mentions | umls-concept:C0162638 | lld:lifeskim |
| pubmed-article:12642862 | lifeskim:mentions | umls-concept:C1514485 | lld:lifeskim |
| pubmed-article:12642862 | pubmed:issue | 11 | lld:pubmed |
| pubmed-article:12642862 | pubmed:dateCreated | 2003-3-18 | lld:pubmed |
| pubmed-article:12642862 | pubmed:abstractText | Smac (or DIABLO) is a recently identified, novel proapoptotic molecule, which is released from mitochondria into the cytosol during apoptosis. Smac functions by eliminating the caspase-inhibitory properties of the inhibitors of apoptosis proteins (IAP), particularly XIAP. In this study, we stably transfected both full-length (FL) and mature (MT) Smac genes into the K562 and CEM leukaemic cell lines. Both FL and MT Smac transfectants increased the sensitivity of leukaemic cells to UV light-induced apoptosis and the activation of caspase-9 and caspase-3. Purified cytosol from the mature Smac transfectants, or the addition of human recombinant Smac protein or N-7 peptide into nontransfected cytosol, showed an increased sensitivity to cytochrome c-induced activation of caspase-3. The mature Smac enhanced the susceptibility of both K562 and CEM cells to TRAIL-induced apoptosis. Overexpression of the mature Smac protein also inhibited proliferation, as detected by reduced colony formation and Ki-67 expression in leukaemic cells. Cell cycle analysis revealed that Smac transfectants displayed significant G0/G1 arrest and reduction in 5-bromo-2'-deoxyuridine (BrdU) incorporation. Smac sensitized human acute myeloid leukaemia blasts to cytochrome c-induced activation of caspase-3. However, Smac failed to overcome Apaf-1-deficiency-mediated resistance to cytochrome c in primary leukaemic blasts. In summary, this study reveals that Smac/DIABLO exhibits a potential role in increasing apoptosis and suppressing proliferation in human leukaemic cells. Importantly, it also indicates that it is crucial to evaluate the levels of Apaf-1 and XIAP proteins in patient samples before using Smac peptide therapy in the treatment of human leukaemia. | lld:pubmed |
| pubmed-article:12642862 | pubmed:language | eng | lld:pubmed |
| pubmed-article:12642862 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:12642862 | pubmed:citationSubset | IM | lld:pubmed |
| pubmed-article:12642862 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:12642862 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:12642862 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:12642862 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:12642862 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:12642862 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:12642862 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:12642862 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:12642862 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:12642862 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:12642862 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:12642862 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:12642862 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:12642862 | pubmed:month | Mar | lld:pubmed |
| pubmed-article:12642862 | pubmed:issn | 0950-9232 | lld:pubmed |
| pubmed-article:12642862 | pubmed:author | pubmed-author:OsL OLO | lld:pubmed |
| pubmed-article:12642862 | pubmed:author | pubmed-author:SrinivasulaSr... | lld:pubmed |
| pubmed-article:12642862 | pubmed:author | pubmed-author:AlnemriEmad... | lld:pubmed |
| pubmed-article:12642862 | pubmed:author | pubmed-author:NewlandAdrian... | lld:pubmed |
| pubmed-article:12642862 | pubmed:author | pubmed-author:KelseyStephen... | lld:pubmed |
| pubmed-article:12642862 | pubmed:author | pubmed-author:PatwariYasmee... | lld:pubmed |
| pubmed-article:12642862 | pubmed:author | pubmed-author:AgrawalSamir... | lld:pubmed |
| pubmed-article:12642862 | pubmed:issnType | Print | lld:pubmed |
| pubmed-article:12642862 | pubmed:day | 20 | lld:pubmed |
| pubmed-article:12642862 | pubmed:volume | 22 | lld:pubmed |
| pubmed-article:12642862 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:12642862 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:12642862 | pubmed:pagination | 1589-99 | lld:pubmed |
| pubmed-article:12642862 | pubmed:dateRevised | 2008-5-14 | lld:pubmed |
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| pubmed-article:12642862 | pubmed:meshHeading | pubmed-meshheading:12642862... | lld:pubmed |
| pubmed-article:12642862 | pubmed:year | 2003 | lld:pubmed |
| pubmed-article:12642862 | pubmed:articleTitle | Role of Smac in human leukaemic cell apoptosis and proliferation. | lld:pubmed |
| pubmed-article:12642862 | pubmed:affiliation | Department of Haematology/Oncology, St Bartholomew's, The Royal School of Medicine and Dentistry, London El 2AD, UK. L.jia@mul.ac.uk | lld:pubmed |
| pubmed-article:12642862 | pubmed:publicationType | Journal Article | lld:pubmed |
| pubmed-article:12642862 | pubmed:publicationType | Research Support, Non-U.S. Gov't | lld:pubmed |
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