Abstract
Hypoxia and other adverse conditions are commonly encountered by rapidly growing cells. The RNA-binding protein RBM3 (RNA-binding motif protein 3), which is transcriptionally induced by low temperature and hypoxia, has recently been implicated in survival of colon cancer cells by mechanisms involving cyclooxygenase-2 (COX-2) signaling. Immunohistochemically, we found strong RBM3 expression in a variety of malignant and proliferating tissues but low expression in resting and terminally differentiated cells. RBM3 expression in fibroblasts and human embryonal kidney (HEK293) cells subjected to serum deprivation or contact inhibition closely paralleled proliferation rates, assessed by real-time RT-PCR and immunoblotting. siRNA-mediated RBM3 knockdown reduced cell viability and finally led to cell death, which did not involve caspase-3-mediated apoptosis, cell cycle arrest, or COX-2 regulation. In contrast, RBM3 over-expression rescued cells from death under serum starvation. This was associated with increased translation rates, as measured by 14C serine and 3H phenylalanine incorporation. Together, RBM3 is a critical factor providing cellular survival advantages in an adverse microenvironment presumably by restoring translation efficacy.
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Abbreviations
- COX-2:
-
cyclooxygenase-2
- HEK293:
-
human embryonal kidney
- HT29:
-
human colon adenocarcinoma cells
- K562:
-
human chronic myeloid leukemia cells
- MTA:
-
multitissue Array
- RBM3:
-
RNA-binding motif protein 3
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Acknowledgements
We are grateful to Barbara Stalder, Molecular Pathology Section, Institute of Pathology, Basel University Hospital, for production of the tissue array and excellent performance of immunohistochemical procedures. We thank Dr. Terttu Suormala for expert technical assistance in determination of protein synthesis, Metabolic Unit, University Children's Hospital, Basel.
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Supported by grants from the Wilhelm-Sander-Foundation (2004.162.1), Munich, Germany, and the Bangerter-Rhyner-Foundation, Bern, Switzerland.
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Wellmann, S., Truss, M., Bruder, E. et al. The RNA-Binding Protein RBM3 Is Required for Cell Proliferation and Protects Against Serum Deprivation-Induced Cell Death. Pediatr Res 67, 35–41 (2010). https://doi.org/10.1203/PDR.0b013e3181c13326
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DOI: https://doi.org/10.1203/PDR.0b013e3181c13326
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