| pubmed-article:17108124 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:17108124 | lifeskim:mentions | umls-concept:C0212694 | lld:lifeskim |
| pubmed-article:17108124 | lifeskim:mentions | umls-concept:C0031715 | lld:lifeskim |
| pubmed-article:17108124 | lifeskim:mentions | umls-concept:C1326205 | lld:lifeskim |
| pubmed-article:17108124 | lifeskim:mentions | umls-concept:C1149301 | lld:lifeskim |
| pubmed-article:17108124 | lifeskim:mentions | umls-concept:C1511545 | lld:lifeskim |
| pubmed-article:17108124 | pubmed:issue | 22 | lld:pubmed |
| pubmed-article:17108124 | pubmed:dateCreated | 2006-11-19 | lld:pubmed |
| pubmed-article:17108124 | pubmed:abstractText | Insulin-like growth factor (IGF) binding protein-3 (IGFBP-3) promotes apoptosis of cancer cells by both IGF-dependent and IGF-independent mechanisms. In vitro phosphorylation of IGFBP-3 by DNA-dependent protein kinase (DNA-PK) has been reported but with unknown functional relevance. Using a chemical inhibitor for DNA-PK in prostate cancer cells and a paired system of glioblastoma cell lines that either lack or express DNA-PK, we show that the apoptosis-promoting and growth-inhibitory actions of IGFBP-3 are completely abrogated in the absence of catalytically active DNA-PK. In the absence of DNA-PK activity, IGFBP-3 has reduced nuclear accumulation and is unable to bind its nuclear binding partner retinoid X receptor (RXR) alpha. We assessed the importance of the three potential DNA-PK phosphorylation sites in IGFBP-3 using PCR-based site-directed mutagenesis. When transfected into 22RV1 cells, IGFBP-3-S165A and IGFBP-3-T170A functioned in an identical manner to wild-type IGFBP-3 to induce apoptosis. In contrast, IGFBP-3-S156A was unable to promote apoptosis and exhibited reduced nuclear accumulation, suggesting a key role for DNA-PK-dependent phosphorylation in the regulation of IGFBP-3 action. These studies reveal a novel regulatory mechanism for the actions of IGFBP-3 in prostate cancer and show phosphorylation of Ser(156) to be functionally critical in its apoptosis-inducing actions. | lld:pubmed |
| pubmed-article:17108124 | pubmed:grant | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:17108124 | pubmed:grant | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:17108124 | pubmed:grant | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:17108124 | pubmed:language | eng | lld:pubmed |
| pubmed-article:17108124 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:17108124 | pubmed:citationSubset | IM | lld:pubmed |
| pubmed-article:17108124 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:17108124 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:17108124 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:17108124 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:17108124 | pubmed:month | Nov | lld:pubmed |
| pubmed-article:17108124 | pubmed:issn | 0008-5472 | lld:pubmed |
| pubmed-article:17108124 | pubmed:author | pubmed-author:CohenPinchasP | lld:pubmed |
| pubmed-article:17108124 | pubmed:author | pubmed-author:LeeKuk-WhaKW | lld:pubmed |
| pubmed-article:17108124 | pubmed:author | pubmed-author:LiuBingrongB | lld:pubmed |
| pubmed-article:17108124 | pubmed:author | pubmed-author:CobbLaura JLJ | lld:pubmed |
| pubmed-article:17108124 | pubmed:issnType | Print | lld:pubmed |
| pubmed-article:17108124 | pubmed:day | 15 | lld:pubmed |
| pubmed-article:17108124 | pubmed:volume | 66 | lld:pubmed |
| pubmed-article:17108124 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:17108124 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:17108124 | pubmed:pagination | 10878-84 | lld:pubmed |
| pubmed-article:17108124 | pubmed:dateRevised | 2009-11-19 | lld:pubmed |
| pubmed-article:17108124 | pubmed:meshHeading | pubmed-meshheading:17108124... | lld:pubmed |
| pubmed-article:17108124 | pubmed:meshHeading | pubmed-meshheading:17108124... | lld:pubmed |
| pubmed-article:17108124 | pubmed:meshHeading | pubmed-meshheading:17108124... | lld:pubmed |
| pubmed-article:17108124 | pubmed:meshHeading | pubmed-meshheading:17108124... | lld:pubmed |
| pubmed-article:17108124 | pubmed:meshHeading | pubmed-meshheading:17108124... | lld:pubmed |
| pubmed-article:17108124 | pubmed:meshHeading | pubmed-meshheading:17108124... | lld:pubmed |
| pubmed-article:17108124 | pubmed:meshHeading | pubmed-meshheading:17108124... | lld:pubmed |
| pubmed-article:17108124 | pubmed:meshHeading | pubmed-meshheading:17108124... | lld:pubmed |
| pubmed-article:17108124 | pubmed:meshHeading | pubmed-meshheading:17108124... | lld:pubmed |
| pubmed-article:17108124 | pubmed:meshHeading | pubmed-meshheading:17108124... | lld:pubmed |
| pubmed-article:17108124 | pubmed:meshHeading | pubmed-meshheading:17108124... | lld:pubmed |
| pubmed-article:17108124 | pubmed:meshHeading | pubmed-meshheading:17108124... | lld:pubmed |
| pubmed-article:17108124 | pubmed:year | 2006 | lld:pubmed |
| pubmed-article:17108124 | pubmed:articleTitle | Phosphorylation by DNA-dependent protein kinase is critical for apoptosis induction by insulin-like growth factor binding protein-3. | lld:pubmed |
| pubmed-article:17108124 | pubmed:affiliation | Division of Pediatric Endocrinology, Mattel Children's Hospital at University of California at Los Angeles, David Geffen School of Medicine, Los Angeles, California, USA. | lld:pubmed |
| pubmed-article:17108124 | pubmed:publicationType | Journal Article | lld:pubmed |
| pubmed-article:17108124 | pubmed:publicationType | Research Support, U.S. Gov't, Non-P.H.S. | lld:pubmed |
| pubmed-article:17108124 | pubmed:publicationType | Research Support, N.I.H., Extramural | lld:pubmed |
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