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LRP130, also known as LRPPRC, was first identified as a highly expressed transcript in a hepatocellular carcinoma cell line, HepG2. Subsequently, it has been revealed to be over-expressed in various other types of human cancer cell lines as well (our unpublished data). Over-expression of LRP130, therefore, could play some beneficial role in tumor cell growth, however, the details of biological functions still remain unsolved. We recently demonstrated LRP130 to be a novel type of RNA-binding protein, mainly localized in the cytoplasm especially in the outer nuclear and endoplasmic reticulum membranes, which interacts with mRNA/mRNP complexes at these sites. To further clarify the biological role of LRP130, interacting proteins in culture cells were immunoprecipitated with an anti-LRP130 antibody and their amino acid sequences were partially determined by LC/MS/MS analyses. Interestingly, an RNA-binding protein, hnPNP K, was showed to interact with LRP130 in an RNA-dependent manner. A considerable number of other RNA-binding proteins were also co-precipitated as candidate partners. Since one of the major functions of hnRNP K in the cytoplasm is its involvement in stability and translation of a subset of mRNA species, we attempted to clarify whether LRP130 could also be involved in translational regulation of some specific mRNA species in vivo. The cytoplasmic LRP130 in HeLa cells was co-fractionated with polysomes using sucrose gradient sedimentation. This co-localization was substantially inhibited by treatment of the cells with an mTOR kinase inhibitor, rapamycin, which is well known to repress the 5’ Cap-dependent mRNA translation. In contrast, the amount of LRP130 in polysome fractions was markedly increased by treatment of the HeLa cells with insulin, a potent stimulator of the mTOR signaling pathway. About 60 mRNA species, including those encoding cell cycle regulators and cell motility and chromatin maintenance proteins, have been identified thus far as binding to LRP130 in vivo using RNP immunoprecipitation (RIP) and subsequent GeneChip® (Affymetrix) analyses. Our results strongly suggest that LRP130 could serve as a downstream effector of the mTOR signaling pathway and thereby modulate mRNA translation activated by various growth factors and oncogenic stimuli.

[Proc Amer Assoc Cancer Res, Volume 46, 2005]