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PAPA-1 Is a nuclear binding partner of IGFBP-2 and modulates its growth-promoting actions.

ABSTRACT: 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.

SUBMITTER: Miyako K

PROVIDER: S-EPMC2646620 | biostudies-literature | 2009 Feb

REPOSITORIES: biostudies-literature

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PAPA-1 Is a nuclear binding partner of IGFBP-2 and modulates its growth-promoting actions.

Miyako Kenichi K Cobb Laura J LJ Francis Malik M Huang Alden A Peng Bonnie B Pintar John E JE Ariga Hiroyoshi H Cohen Pinchas P

Molecular endocrinology (Baltimore, Md.) 20081218 2

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 expressio ...[more]

PMID: 19095771

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Dataset Information

PAPA-1 Is a nuclear binding partner of IGFBP-2 and modulates its growth-promoting actions.

Publications

PAPA-1 Is a nuclear binding partner of IGFBP-2 and modulates its growth-promoting actions.

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