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Inhibitor of apoptosis proteins (IAPs) prevent apoptosis through direct inhibition of caspases. The serine protease HtrA2/Omi has an amino-terminal IAP interaction motif like that found in Reaper, which displaces IAPs from caspases, leading to enhanced caspase activity. The cell death-promoting properties of HtrA2/Omi are not only exerted through its(More)
The Myc family proteins are potent oncogenes that can activate and repress a very large number of cellular target genes. The amino terminus of Myc contains a transactivation domain that can recruit a number of nuclear cofactors with diverse activities. Functional studies link transactivation to the ability of Myc to promote normal cell proliferation and for(More)
Methylation of the mRNA 5' guanosine cap is essential for efficient gene expression. The 5' methyl cap binds to eIF4E, which is the first step in the recruitment of mRNA to the 40S ribosomal subunit. To investigate whether mRNA cap methylation is regulated in a gene-specific manner, we established a method to detect the relative level of cap methylation on(More)
Myc controls the metabolic reprogramming that supports effector T cell differentiation. The expression of Myc is regulated by the T cell antigen receptor (TCR) and pro-inflammatory cytokines such as interleukin-2 (IL-2). We now show that the TCR is a digital switch for Myc mRNA and protein expression that allows the strength of the antigen stimulus to(More)
Myc promotes both normal cell proliferation and oncogenic transformation through the activation and repression of target genes. The c-Myc-S protein is a truncated form of c-Myc that is produced in some cells from translation initiation at an internal AUG codon. We report that c-Myc-S and a similar truncated form of N-MycWT can fully rescue the proliferation(More)
Krüppel-like factor 2 (KLF2) is a transcription factor that is highly expressed in quiescent T lymphocytes and downregulated in effector T cells. We now show that antigen receptor engagement downregulates KLF2 expression in a graded response determined by the affinity of T cell antigen receptor (TCR) ligand and the integrated activation of protein kinase B(More)
Caspase activation resulting from cytochrome c release from the mitochondria is an essential component of the mechanism of apoptosis initiated by a range of factors. The activation of Bid by caspase-8 in this pathway promotes further cytochrome c release, thereby completing a positive feedback loop of caspase activation. Although the identity of the(More)
MYC is a potent oncogene that drives unrestrained cell growth and proliferation. Shortly after its discovery as an oncogene, the MYC protein was recognized as a sequence-specific transcription factor. Since that time, MYC oncogene research has focused on the mechanism of MYC-induced transcription and on the identification of MYC transcriptional target(More)
Myc is a transcription factor which is dependent on its DNA binding domain for transcriptional regulation of target genes. Here, we report the surprising finding that Myc mutants devoid of direct DNA binding activity and Myc target gene regulation can rescue a substantial fraction of the growth defect in myc(-/-) fibroblasts. Expression of the Myc(More)
BACKGROUND The MYC oncogene contributes to induction and growth of many cancers but the full spectrum of the MYC transcriptional response remains unclear. METHODOLOGY/PRINCIPAL FINDINGS Using microarrays, we conducted a detailed kinetic study of genes that respond to MYCN or MYCNDeltaMBII induction in primary human fibroblasts. In parallel, we determined(More)