Abstract
BackgroundRegulation of mRNAs is one way to control protein levels and thereby important cellular processes such as growth, invasion and apoptosis. G3BPs constitute a family of mRNA-binding proteins, shown to be overexpressed in several cancer types, including breast, colon and pancreas cancer. G3BP has been reported to both stabilize and induce degradation of specific mRNAs.ResultsHere, we show that G3BP1, but not G3BP2, supports proliferation of several breast cancer cell lines. Global gene expression analyses of G3BP1- and G3BP2-depleted cells indicate that primarily G3BP1, and much less G3BP2, influences mRNA expression levels. Peripheral myelin protein 22 (PMP22) was one gene that was significantly influenced by G3BP1 depletion which led to a 2–3 fold increased expression. Depletion of PMP22 resulted in increased proliferation and the G3BP1-mediated effect on proliferation was not seen upon PMP22-depletion.ConclusionsThis indicates a novel role for G3BP1 in the regulation of cell proliferation in breast cancer cells, perhaps via a regulatory effect on PMP22 expression.
Highlights
Regulation of mRNAs is one way to control protein levels and thereby important cellular processes such as growth, invasion and apoptosis
We found that G3BP1 to a larger extent than G3BP2 influences mRNA expression levels and breast cancer cell proliferation
G3BP1 depletion decreases cell proliferation To elucidate the role of Ras-GTPase activating protein SH3 domain binding proteins (G3BP) proteins in breast cancer cell growth, we analyzed the effects of G3BP depletion on cell proliferation and death
Summary
Regulation of mRNAs is one way to control protein levels and thereby important cellular processes such as growth, invasion and apoptosis. G3BPs constitute a family of mRNA-binding proteins, shown to be overexpressed in several cancer types, including breast, colon and pancreas cancer. All G3BP proteins contain a RNA recognition motif (RRM) and have been shown to have both mRNA-stabilizing effects, exemplified by TAU mRNA [6] as well as mRNAdegrading effects, as demonstrated for c-MYC [7], BART [8], CTNNB1 [9], ATP5B [10], IGF-II, and GAS5 [11].The degrading effect has been indicated to be mediated by endonuclease activity of the G3BPs themselves [12]. A potential role for G3BPs in cancer is indicated by the finding that they have been found to be expressed at high levels in many different tumor types e.g. breast [13,15,16], pancreas [8], thyroid, colon, head and neck tumors [13] as well as in several cancer cell lines [8,13]
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