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Control of mRNA translation plays a fundamental role in many aspects of cell metabolism. It constitutes a critical step in the control of gene expression, and consequently cell growth, proliferation and differentiation. Translation is regulated in response to nutrient availability, hormones, mitogenic and growth factor stimulation and is coupled with cell(More)
Over the years, studies have focused on the transcriptional regulation of oncogenesis. More recently, a growing emphasis has been placed on translational control. The Ras and Akt signal transduction pathways play a critical role in regulating mRNA translation and cellular transformation. The question arises: How might the Ras and Akt signaling pathways(More)
The differentiation of B cells into immunoglobulin-secreting plasma cells is controlled by two transcription factors, Blimp-1 and XBP1. By gene expression profiling, we defined a set of genes whose induction during mouse plasmacytic differentiation is dependent on Blimp-1 and/or XBP1. Blimp-1-deficient B cells failed to upregulate most plasma cell-specific(More)
The mammalian target of rapamycin complex 1 (mTORC1) integrates mitogen and nutrient signals to control cell proliferation and cell size. Hence, mTORC1 is implicated in a large number of human diseases--including diabetes, obesity, heart disease, and cancer--that are characterized by aberrant cell growth and proliferation. Although eukaryotic translation(More)
Translational regulation plays a critical role in the control of cell growth and proliferation. A key player in translational control is eIF4E, the mRNA 5' cap-binding protein. Aberrant expression of eIF4E promotes tumorigenesis and has been implicated in cancer development and progression. The activity of eIF4E is dysregulated in cancer. Regulation of(More)
BACKGROUND Translation deregulation is an important mechanism that causes aberrant cell growth, proliferation and survival. eIF4E, the mRNA 5' cap-binding protein, plays a major role in translational control. To understand how eIF4E affects cell proliferation and survival, we studied mRNA targets that are translationally responsive to eIF4E. (More)
Miscoordination of growth and proliferation with the cellular stress response can lead to tumorigenesis. Mammalian target of rapamycin (mTOR), a central cell growth controller, is highly activated in some malignant neoplasms, and its clinical implications are under extensive investigation. We show that constitutive mTOR activity amplifies p53 activation, in(More)
Messenger RNA translation or protein synthesis, is a fundamental biological process affecting cell growth, survival and proliferation. Initiation is the rate limiting and hence the most regulated step of translation. In eukaryotes, translation initiation is facilitated by multiple protein factors collectively called eIFs (for eukaryotic translation(More)
We have examined motor control in normal and shiverer mutant mice using the rotarod assay, a forced motor activity which tests for balance and co-ordination. Shiverer mice carry a deletion of the myelin basic protein (MBP) gene, resulting in CNS dysmyelination and characteristic motor dysfunction. Homozygous mutant mice had a significant increase in(More)
The mammalian target of rapamycin (mTOR) and Akt proteins regulate various steps of muscle development and growth, but the physiological relevance and the downstream effectors are under investigation. Here we show that S6 kinase 1 (S6K1), a protein kinase activated by nutrients and insulin-like growth factors (IGFs), is essential for the control of muscle(More)