Source:http://linkedlifedata.com/resource/pubmed/id/20729913
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
48
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pubmed:dateCreated |
2010-12-2
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pubmed:abstractText |
The mechanism underlying curcumin (diferuloylmethane) resistance is still largely unknown. Here we employed proteomic approach to identify the Siah-interacting protein (SIP) as a candidate for detailed study, because the spot intensity of SIP on a two-dimensional gel displayed 70-90% reduction in curcumin-sensitive cells, but remained unchanged in curcumin-resistant sublines, after curcumin treatment. Both gain- and loss-of-function studies revealed that SIP promoted curcumin-induced apoptosis. Moreover, SIP underwent phosphorylation and nuclear translocation in curcumin-sensitive but not resistant cells, upon curcumin exposure. The nuclear translocation of SIP was remarkably impaired when a putative nuclear localization sequence (NLS, amino acid (aa) 143-159) was deleted or the serine 141 was mutated into alanine, whereas truncation of the N-terminal region (aa 1-43) obviously increased the nuclear import of SIP. In accordance with their nuclear localization, N-terminal truncation significantly enhanced the proapoptotic effect of SIP, whereas NLS deletion or Ser141Ala mutation attenuated the apoptosis-promoting activity of both wild-type- and N-terminal truncated-SIP. These data suggest that SIP plays a role in apoptosis and curcumin resistance, and the function of SIP may be regulated by different motifs, such as the NLS, N-terminal region and serine 141. Our findings provide new insights into the biological significance of SIP and the mechanisms of drug resistance.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antineoplastic Agents,
http://linkedlifedata.com/resource/pubmed/chemical/CACYBP protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Curcumin,
http://linkedlifedata.com/resource/pubmed/chemical/Tetradecanoylphorbol Acetate
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pubmed:status |
MEDLINE
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pubmed:month |
Dec
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pubmed:issn |
1476-5594
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pubmed:author | |
pubmed:issnType |
Electronic
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pubmed:day |
2
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pubmed:volume |
29
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
6357-66
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pubmed:meshHeading |
pubmed-meshheading:20729913-Active Transport, Cell Nucleus,
pubmed-meshheading:20729913-Antineoplastic Agents,
pubmed-meshheading:20729913-Apoptosis,
pubmed-meshheading:20729913-Calcium-Binding Proteins,
pubmed-meshheading:20729913-Cell Line, Tumor,
pubmed-meshheading:20729913-Curcumin,
pubmed-meshheading:20729913-Drug Resistance, Neoplasm,
pubmed-meshheading:20729913-Humans,
pubmed-meshheading:20729913-Phosphorylation,
pubmed-meshheading:20729913-Tetradecanoylphorbol Acetate
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pubmed:year |
2010
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pubmed:articleTitle |
Identification of Siah-interacting protein as a potential regulator of apoptosis and curcumin resistance.
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pubmed:affiliation |
Key Laboratory of Gene Engineering of the Ministry of Education, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, PR China.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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