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Cell growth (accumulation of mass) needs to be coordinated with metabolic processes that are required for the synthesis of macromolecules. The PI3-kinase/Akt signaling pathway induces cell growth via activation of complex 1 of the target of rapamycin (TORC1). Here we show that Akt-dependent lipogenesis requires mTORC1 activity. Furthermore, nuclear(More)
The VRK1 kinase is a novel Ser-Thr kinase in the human kinome that diverged from the casein kinase 1 branch. These kinases phosphorylate transcription factors related to stress responses, such as p53. In this report we have studied the phosphorylation of the transcription factor c-Jun in its N-terminal region. The VRK1 protein phosphorylates c-Jun with a Km(More)
Hypoxia represents a major stress that requires an immediate cellular response in which different signaling pathways participate. Hypoxia induces an increase in the activity of TAK1, an atypical mitogen-activated protein kinase kinase kinase (MAPKKK), which responds to oxidative stress by triggering cascades leading to the activation of c-Jun N-terminal(More)
BACKGROUND Cellular biological responses to specific stimulation are determined by a balance among signaling pathways. Protein interactions are likely to modulate these pathways. Vaccinia-related kinase-2 (VRK2) is a novel human kinase that can modulate different signaling pathways. PRINCIPAL FINDINGS We report that in vivo, the activity of JIP1-JNK(More)
In recent years several reports have linked mTORC1 (mammalian target of rapamycin complex 1) to lipogenesis via the SREBPs (sterol-regulatory-element-binding proteins). SREBPs regulate the expression of genes encoding enzymes required for fatty acid and cholesterol biosynthesis. Lipid metabolism is perturbed in some diseases and SREBP target genes, such as(More)
Clear cell renal cell carcinoma (ccRCC) is the most common pathological subtype of kidney cancer. Here, we integrated an unbiased genome-wide RNA interference screen for ccRCC survival regulators with an analysis of recurrently overexpressed genes in ccRCC to identify new therapeutic targets in this disease. One of the most potent survival regulators, the(More)
BACKGROUND Candidate biomarkers have been identified for clear cell renal cell carcinoma (ccRCC) patients, but most have not been validated. OBJECTIVE To validate published ccRCC prognostic biomarkers in an independent patient cohort and to assess intratumour heterogeneity (ITH) of the most promising markers to guide biomarker optimisation. DESIGN,(More)
Defining mechanisms that generate intratumour heterogeneity and branched evolution may inspire novel therapeutic approaches to limit tumour diversity and adaptation. SETD2 (Su(var), Enhancer of zeste, Trithorax-domain containing 2) trimethylates histone-3 lysine-36 (H3K36me3) at sites of active transcription and is mutated in diverse tumour types, including(More)
Suppression of detachment-induced cell death, known as anoikis, is an essential step for cancer metastasis to occur. We report here that expression of KLF12, a member of the Kruppel-like family of transcription factors, is downregulated in lung cancer cell lines that have been selected to grow in the absence of cell adhesion. Knockdown of KLF12 in parental(More)
TO THE EDITOR: Significant progress in systemic therapy of met-astatic renal cell carcinoma (mRCC) has been made over the last 5 years, with a plethora of targeted agents currently approved in different clinical settings. However, not all mRCC patients respond to treatment with these drugs and currently there are no validated bio-markers to predict clinical(More)