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Programmed destruction of regulatory proteins through the ubiquitin-proteasome system is a widely used mechanism for controlling signalling pathways. Cullins are proteins that function as scaffolds for modular ubiquitin ligases typified by the SCF (Skp1-Cul1-F-box) complex. The substrate selectivity of these E3 ligases is dictated by a specificity module(More)
We performed a genome-wide analysis of aberrant DNA methylation in chronic lymphocytic leukemia (CLL) using methylated CpG island amplification (MCA) coupled with a promoter microarray. We identified 280 potential targets of aberrant DNA methylation in CLL. These genes were located more frequently in chromosomes 19 (16%, p=0.001), 16 (11%, p=0.001), 17(More)
Blockade of immune checkpoints is emerging as a new form of anticancer therapy. We studied the expression of programmed death ligand 1 (PD-L1), PD-L2, programmed death 1 (PD-1) and cytotoxic T lymphocyte-associated antigen 4 (CTLA4) mRNA in CD34+ cells from myelodysplastic syndrome (MDS), chronic myelomonocytic leukemia (CMML) and acute myeloid leukemia(More)
p220(NPAT) is a substrate of cyclin E/Cdk2 that localizes in nuclear organelles called Cajal bodies in a cell cycle-regulated manner. In normal diploid fibroblasts, p220 is concentrated in two Cajal bodies tethered to histone gene clusters at chromosome 6p21 during G(1), S, and G(2) phases and two additional Cajal bodies tethered to histone genes at 1q21(More)
Cyclin E/Cdk2, a central regulator of the G1/S transition, coordinates multiple cell cycle events, including DNA replication, centrosome duplication, and activation of the E2F transcriptional program. Recent studies suggest a role for cyclin E/Cdk2 in activation of histone transcription during S phase via the Cajal body-associated protein p220NPAT, and in(More)
Histone deacetylase (HDAC) inhibitors have been shown to induce cell cycle arrest, terminal differentiation, and apoptosis in a broad spectrum of human tumors and animal xenograft models. JNJ-26481585 is a hydroxamic acid derivative, second-generation pan-HDAC inhibitor that has demonstrated high potency in preclinical studies. In the current study, we(More)
Myelodysplastic syndromes (MDS) are characterized by impaired proliferation and differentiation of hematopoietic stem cells. The participation of toll-like receptor (TLR)-mediated signaling in MDS is well documented. Increased TLR signaling leads to the constitutive activation of NF-κB, which mediates inflammation, cell proliferation and apoptosis. In(More)
Monitoring autophagic flux is important for the analysis of autophagy. Tandem fluorescent-tagged LC3 (mRFP-EGFP-LC3) is a convenient assay for monitoring autophagic flux based on different pH stability of EGFP and mRFP fluorescent proteins. However, it has been reported that there is still weak fluorescence of EGFP in acidic environments (pH between 4 and(More)
Mechanisms of action and resistance of histone deacetylase inhibitors (HDACIs) are not well understood. A gene expression analysis performed in a phase 1 trial of vorinostat in leukemia indicated that overexpression of genes involved in antioxidant defense was associated with clinical resistance. We hypothesized that nonepigenetic mechanisms may be involved(More)
Genome replication in eukaryotic cells necessitates the stringent coupling of histone biosynthesis with the onset of DNA replication at the G1/S phase transition. A fundamental question is the mechanism that links the restriction (R) point late in G1 with histone gene expression at the onset of S phase. Here we demonstrate that HiNF-P, a transcriptional(More)