Publications by authors named "Dritan Liko"

Protein histidine phosphorylation (pHis) is a posttranslational modification involved in cell cycle regulation, ion channel activity and phagocytosis. Using novel monoclonal antibodies to detect pHis, we previously reported that the loss of the histidine phosphatase LHPP (phospholysine phosphohistidine inorganic pyrophosphate phosphatase) results in elevated pHis levels in hepatocellular carcinoma. Here, we show that intestinal inflammation correlates with the loss of LHPP in dextran sulfate sodium (DSS)-treated mice and in inflammatory bowel disease (IBD) patients.

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Background: Genetic aberrations in hepatocellular carcinoma (HCC) are well known, but the functional consequences of such aberrations remain poorly understood.

Results: Here, we explored the effect of defined genetic changes on the transcriptome, proteome and phosphoproteome in twelve tumors from an mTOR-driven hepatocellular carcinoma mouse model. Using Network-based Integration of multi-omiCS data (NetICS), we detected 74 'mediators' that relay via molecular interactions the effects of genetic and miRNA expression changes.

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Loss of the tumor suppressor tuberous sclerosis complex 1 () in the liver promotes gluconeogenesis and glucose intolerance. We asked whether this could be attributed to aberrant expression of small RNAs. We performed small-RNA sequencing on liver of -knockout mice, and found that miRNAs of the delta-like homolog 1 ()-deiodinase iodothyronine type III () locus are up-regulated in an mTORC1-dependent manner.

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Article Synopsis
  • RNA polymerase III (Pol-III) is crucial for making tRNAs and small RNAs, and its deregulation is linked to cancer, but its in vivo role wasn't well understood.
  • Researchers manipulated the Brf1 transcription factor that helps Pol-III work, finding that knocking out Brf1 caused embryos to die, while mice with one functional copy were healthy.
  • Conditional deletion of Brf1 in certain organs led to cell death and disrupted tissue balance, but Brf1's variation did not influence cancer development, indicating Brf1 is vital for tissue health but doesn’t directly drive cancer in the pancreas or gut.
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Histidine phosphorylation, the so-called hidden phosphoproteome, is a poorly characterized post-translational modification of proteins. Here we describe a role of histidine phosphorylation in tumorigenesis. Proteomic analysis of 12 tumours from an mTOR-driven hepatocellular carcinoma mouse model revealed that NME1 and NME2, the only known mammalian histidine kinases, were upregulated.

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The cell's repertoire of transfer RNAs (tRNAs) has been linked to cancer. Recently, the level of the initiator methionine tRNA (tRNA) in stromal fibroblasts has been shown to influence extracellular matrix (ECM) secretion to drive tumour growth and angiogenesis. Here we show that increased tRNA within cancer cells does not influence tumour growth, but drives cell migration and invasion via a mechanism that is independent from ECM synthesis and dependent on α5β1 integrin and levels of the translation initiation ternary complex.

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Target of rapamycin (TOR) is a highly conserved protein kinase that plays a key role in mediating cell growth and homeostasis. It is activated by nutrients, growth factors, and cellular energy levels to control a number of anabolic and catabolic processes. It is a validated drug target implicated in a variety of diseases.

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Epigenetic control is an important aspect of gene regulation. Despite detailed understanding of protein-coding gene expression, the transcription of noncoding RNA genes by RNA polymerase III (Pol III) is less well characterized. Here we profile the epigenetic features of Pol III target genes throughout the human genome.

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Addition of glucose to quiescent Saccharomyces cerevisiae cells causes the immediate induction of approximately 1000 genes. These genes include ribosomal proteins (RP) and non-RP genes needed for ribosome production and other growth processes. RRPE sequence elements are commonly found 5' of non-RP growth gene ORFs, and Stb3 has recently been identified as an RRPE binding protein.

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Nutrient repletion leads to substantial restructuring of the transcriptome in Saccharomyces cerevisiae. The expression levels of approximately one-third of all S. cerevisiae genes are altered at least twofold when a nutrient-depleted culture is transferred to fresh medium.

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Transfer of quiescent Saccharomyces cerevisiae cells to fresh medium rapidly induces hundreds of genes needed for growth. A large subset of these genes is regulated via a DNA sequence motif known as the ribosomal RNA processing element (RRPE). However, no RRPE-binding proteins have been identified.

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Azf1 activates CLN3 transcription in Saccharomyces cerevisiae cells growing in glucose. Paradoxically, other studies have shown Azf1 to be almost undetectable in glucose-grown cells. Microarray experiments showed that Azf1 activates nonoverlapping gene sets in different carbon sources: in glucose, Azf1 activates carbon and energy metabolism genes, and in glycerol-lactate, Azf1 activates genes needed for cell wall maintenance.

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