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Cytoprotective alpha crystallins in the regulation of RPE cell proteostasis
SummaryAlphaB‐Crystallin (αBC) is an ubiquitous protein with dual function as a molecular chaperone to preserve proteostasis and as an anti‐apoptotic agent. We studied the regulatory role of αBC in murine models of oxygen‐induced retinopathy (OIR), laser‐induced choroidal neovascularization (CNV) and subretinal fibrosis (SF). αBC KO attenuated retinal NV in OIR as compared to WT. In the laser model, CNV lesion size was significantly reduced in αBC KO vs. WT mice. VEGF increased 8 fold in WT vs. αBC KO on day 3 and 7 post‐laser and VEGF secretion was lower in αBC KO vs. WT. Increased mono (tetra)‐ubiquitin...
Source: Acta Ophthalmologica - September 13, 2016 Category: Opthalmology Authors: R. Kannan Tags: Abstracts from the 2016 European Association for Vision and Eye Research Conference Source Type: research

Abstract A18: Epigenetic profiling uncovers the suppressive role of caveolae in Ewing sarcoma
Ewing sarcoma (ES) is the second most common bone tumor in childhood. ES harbors a characteristic gene translocation that gives rise to a fusion protein, most commonly EWS/FLI1 (EF). Caveolin-1 (CAV1) is a direct target of EF, it is overexpressed in ES and has an oncogenic role. CAV1 and the Polymerase I and transcript release factor (PTRF) interact at the plasma membrane and are essential for caveolae formation. The methylome analysis of ES samples and cell lines revealed a hypermethylation in the N-shore islands of the PTRF promoter compared to normal cells. We hypothesize that, as ES cells have very few caveolae and do ...
Source: Cancer Research - April 3, 2016 Category: Cancer & Oncology Authors: Huertas–Martinez, J., Court, F., Rello–Varona, S., Martin, D. H., Almacellas, O., Sainz–Jaspeado, M., Garcia–Monclus, S., Lagares–Tena, L., Buȷ, R., Hontecillas–Prieto, L., Mateo–Lozano, S., Sastre, A., Azo Tags: Epigenetics Source Type: research

Abstract B50: Actin remodeling confers BRAF inhibitor resistance to melanoma cells through YAP/TAZ activation
ConclusionOur results implicate the actin cytoskeleton in the induction of YAP/TAZ-dependent resistance to vemurafenib, and inhibition of actin remodeling might be a promising synthetic lethal strategy to suppress resistance in BRAF inhibitor therapies.Citation Format: Min Hwan Kim, Joon Kim. Actin remodeling confers BRAF inhibitor resistance to melanoma cells through YAP/TAZ activation. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2015 Nov 5-9; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2015;14(12 Suppl 2):Abstract nr B50.
Source: Molecular Cancer Therapeutics - January 7, 2016 Category: Cancer & Oncology Authors: Kim, M. H., Kim, J. Tags: Drug Resistance and Modifiers: Poster Presentations - Proffered Abstracts Source Type: research

Abstract PR15: ERK2 binds to MYC promoter and induces MYC expression
It has been known since 30 years ago that serum and growth factors induce a dramatic upregulation of MYC expression in quiescent cells, but the molecular mechanism for this effect is unknown. It has been reported that ERK can bind to DNA and modify gene expression (Hu et al., Cell, 2009). We have investigated the possibility that ERK directly upregulates MYC at the transcriptional level. We have found that: (i) Bioinformatic analyses reveal the presence of ERK binding sites (ERK boxes) conserved in human, mice and rat MYC promoters, located at -0.3 kbp, -1 kbp and -1.7 kbp from the transcription star site; (ii) ERK binds t...
Source: Molecular Cancer Research - October 18, 2015 Category: Cancer & Oncology Authors: Quintanilla, A., Rodriguez, J., Garcia-Gutierrez, L., Lorena, A., Crespo, P., Leon., J. Tags: Myc Beyond Cancer: Oral Presentations - Proffered Abstracts Source Type: research