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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
2
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pubmed:dateCreated |
2009-1-27
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pubmed:abstractText |
IGF-binding proteins (IGFBPs) have multiple cellular effects, which occur by both IGF-dependent and -independent mechanisms. IGFBP-2 is involved in the regulation of both normal and carcinogenic cell growth. To further understand the actions of IGFBP-2, we carried out a yeast two-hybrid screen to search for intracellular partner proteins using a human prostate cDNA library. We isolated Pim-1-associated protein-1 (PAP-1)-associated protein-1 (PAPA-1) as an IGFBP-2-binding protein, whose expression and subcellular localization is regulated by both IGFBP-2 and androgens. Coimmunoprecipitation and glutathione S-transferase pull-down assay confirmed the interaction in vitro, and confocal microscopy showed the colocalization of IGFBP-2 and PAPA-1 in the nucleus. Suppression of PAPA-1 by small interfering RNA treatment enhanced the growth-promoting effect of IGFBP-2. Conversely, IGFBP-2-promoted bromodeoxyuridine incorporation into LNCaP cells was abrogated by the simultaneous overexpression of myc-hPAPA-1. Mouse embryonic fibroblasts from IGFBP-2 knockout mouse showed diminished growth activity compared with wild type, and expression of FLAG-mPAPA-1 decreased cell proliferation in IGFBP-2 knockout, but not control mouse embryonic fibroblasts. These studies suggest that the growth-promoting role of IGFBP-2 in prostate cancer is inhibited by its intracellular interaction with PAPA-1.
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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/19095771-10527667,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19095771-10811646,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19095771-10822175,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19095771-10874028,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19095771-10931201,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19095771-10976924,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19095771-11341982,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19095771-12466191,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19095771-12672024,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19095771-12839944,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19095771-14617774,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19095771-14871828,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19095771-15171717,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19095771-15474485,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19095771-15479293,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19095771-15556297,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19095771-15686601,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19095771-15694994,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19095771-16131350,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19095771-16569642,
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http://linkedlifedata.com/resource/pubmed/commentcorrection/19095771-17072950,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19095771-17280861,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19095771-17369847,
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http://linkedlifedata.com/resource/pubmed/commentcorrection/19095771-17606927,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19095771-18276763,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19095771-7514152,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19095771-7519190,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19095771-7682560,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19095771-9215312,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19095771-9660801
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Carrier Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Cell Cycle Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/INO80B protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Insulin-Like Growth Factor Binding...,
http://linkedlifedata.com/resource/pubmed/chemical/Nuclear Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/PAPA-1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-pim-1,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Small Interfering
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pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
0888-8809
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
23
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
169-75
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pubmed:dateRevised |
2010-9-23
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pubmed:meshHeading |
pubmed-meshheading:19095771-Animals,
pubmed-meshheading:19095771-Carrier Proteins,
pubmed-meshheading:19095771-Cell Cycle Proteins,
pubmed-meshheading:19095771-Cell Line, Tumor,
pubmed-meshheading:19095771-Cell Proliferation,
pubmed-meshheading:19095771-Humans,
pubmed-meshheading:19095771-Insulin-Like Growth Factor Binding Protein 2,
pubmed-meshheading:19095771-Male,
pubmed-meshheading:19095771-Mice,
pubmed-meshheading:19095771-Mice, Knockout,
pubmed-meshheading:19095771-Nuclear Proteins,
pubmed-meshheading:19095771-Prostate,
pubmed-meshheading:19095771-Prostatic Neoplasms,
pubmed-meshheading:19095771-Proto-Oncogene Proteins c-pim-1,
pubmed-meshheading:19095771-RNA, Small Interfering,
pubmed-meshheading:19095771-Two-Hybrid System Techniques
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pubmed:year |
2009
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pubmed:articleTitle |
PAPA-1 Is a nuclear binding partner of IGFBP-2 and modulates its growth-promoting actions.
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pubmed:affiliation |
David Geffen School of Medicine at University of California, Los Angeles, California 90095-1752, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, Non-P.H.S.,
Research Support, N.I.H., Extramural
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