Acquisition of Invasiveness by Breast Adenocarcinoma Cells Engages Established Hallmarks and Novel Regulatory Mechanisms.

Background/aim: Proteomics of invasiveness opens a window on the complexity of the metastasis-engaged mechanisms. The extend and types of this complexity require elucidation.

Materials And Methods: Proteomics, immunohistochemistry, immunoblotting, network analysis and systems cancer biology were used to analyse acquisition of invasiveness by human breast adenocarcinoma cells.

21st Century Genetics: Mass Spectrometry of Yeast Telomerase.

Telomerase is a specialized reverse transcriptase that maintains the ends of chromosomes in almost all eukaryotes. The core of telomerase consists of telomerase RNA and the reverse transcriptase that uses a short segment without the RNA to template the addition of telomeric repeats. In addition, one or more accessory proteins are required for telomerase action in vivo.

Proteomics of yeast telomerase identified Cdc48-Npl4-Ufd1 and Ufd4 as regulators of Est1 and telomere length.

Almost 400 genes affect yeast telomere length, including Est1, which is critical for recruitment and activation of telomerase. Here we use mass spectrometry to identify novel telomerase regulators by their co-purification with the telomerase holoenzyme. In addition to all known subunits, over 100 proteins are telomerase associated, including all three subunits of the essential Cdc48-Npl4-Ufd1 complex as well as three E3 ubiquitin ligases.

Translational connection of TGFβ signaling: Phosphorylation of eEF1A1 by TβR-I inhibits protein synthesis.

Transforming growth factor-β (TGFβ) signaling pathways regulate a wide array of cellular activities that are crucial for cell proliferation, apoptosis, migration and differentiation. TGFβ signaling pathways are initiated by ligand-activated TGFβ receptors, with type I TGFβ receptors (TβR-I) kinase being essential for phosphorylation of downstream targets. Until now, a prevalent view was that the TGFβ intracellular signaling targets would regulate transcription.

Phosphorylation of eEF1A1 at Ser300 by TβR-I results in inhibition of mRNA translation.

Background: Transforming growth factor β (TGF-β) is a potent inhibitor of cell proliferation that regulates cell functions by activating specific serine/threonine kinase receptors on the cell surface. Type I TGF-β receptor (TβR-I) is essential for TGF-β signaling, and substrates of TβR-I provide insights into molecular mechanisms of TGF-β signaling.

Results: Here we identify eukaryotic elongation factor 1A1 (eEF1A1) as a novel substrate of TβR-I.

Comparative proteome profiling of MCF10A and 184A1 human breast epithelial cells emphasized involvement of CDK4 and cyclin D3 in cell proliferation.

Acquiring high proliferation rate is crucial for carcinogenic transformation of cells. We report here proteome profiling of human breast epithelial cells with low (184A1) and high (MCF10A) proliferation rates. We identified 183 proteins in 184A1 and 318 proteins in MCF10A cells.

The signaling pathways of Epstein-Barr virus-encoded latent membrane protein 2A (LMP2A) in latency and cancer.

Epstein-Barr virus (EBV) is a ubiquitous virus with infections commonly resulting in a latency carrier state. Although the exact role of EBV in cancer pathogenesis remains not entirely clear, it is highly probable that it causes several lymphoid and epithelial malignancies, such as Hodgkin's lymphoma, NK-T cell lymphoma, Burkitt's lymphoma, and nasopharyngeal carcinoma. EBV-associated malignancies are associated with a latent form of infection, and several of these EBV-encoded latent proteins are known to mediate cellular transformation.

Differential effect of sanguinarine, chelerythrine and chelidonine on DNA damage and cell viability in primary mouse spleen cells and mouse leukemic cells.

Sanguinarine, chelerythrine and chelidonine are isoquinoline alkaloids derived from the greater celandine. They possess a broad spectrum of pharmacological activities. It has been shown that their anti-tumor activity is mediated via different mechanisms, which can be promising targets for anti-cancer therapy.

Dendritic cells heterogeneity and its role in cancer immunity.

Dendritic cells are the most potent 'professional' antigen-presenting cells, with high ability of primary immune response initiation. Dendritic cells originate from bone marrow progenitors, which circulate in peripheral blood and subsequently give rise to immature dendritic cells, which reside in peripheral tissues. When dendritic cells encounter danger signals, they undergo differentiation and maturation; thereafter they migrate to lymphatic tissues, where they synapse with T-cells and initiate primary immune response.

Endings in the middle: current knowledge of interstitial telomeric sequences.

Interstitial telomeric sequences (ITSs) consist of tandem repeats of the canonical telomeric repeat and are common in mammals. They are localized at intrachromosomal sites, including those repeats located close to the centromeres and those found at interstitial sites, i.e.

The telomere length dynamic and methods of its assessment.

Human telomeres are composed of long repeating sequences of TTAGGG, associated with a variety of telomere-binding proteins. Its function as an end-protector of chromosomes prevents the chromosome from end-to-end fusion, recombination and degradation. Telomerase acts as reverse transcriptase in the elongation of telomeres, which prevent the loss of telomeres due to the end replication problems.