Project description:Pre-effector and pre-memory cells resulting from the first CD8+ T cell division in vivo exhibit low and high rates of proteasome degradative activities, respectively. These proteasome-induced metabolic consequences were mediated in part by asymmetric segregation of Myc during cell division. Taken together, these results suggest proteasome activity as a regulator of CD8+ T lymphocyte metabolism and fate specification.
Project description:Regulated proteolysis in eukaryotes relies on the ubiquitin-proteasome system, which is critical to myriad cellular functions, including protein quality control, cell cycle regulation, and DNA repair. Here, we provide evidence that proteasome activity is also essential for maintaining cell identity. This discovery was made by evaluating the impact of losing the ubiquitin-binding activity of proteasome substrate receptor hRpn10/PSMD4. The most dysregulated proteins in cells that express hRpn10 truncated before its ubiquitin interaction motifs (ΔUIM) are transcriptionally altered, with striking overrepresentation of proteins canonically restricted in expression to specific tissues. This dysregulation is partly driven by accumulation of the proteasome substrate anddeubiquitinase OTUD5, a known chromatin and transcriptional regulator. Our results thus identify previously unrecognized proteasome-dependent mechanisms to safeguard cell-type specific gene expression programs and expand proteasome biology to include governance of cell identity.
Project description:We identify numerous miR-203 in vivo targets that are highly enriched for the promotion of cell cycle and cell division. Importantly, individual targets including p63, Skp2 and Msi2 play distinct roles downstream of miR-203 to regulate the cell cycle and long-term proliferation. Together, our findings reveal rapid and widespread impact of miR-203 on the self-renewal program during the epidermal differentiation and provide mechanistic insights for the potent role of miR-203 where coordinated repression of multiple targets is required for the function of this miRNA. We used microarrays to measure transcriptome changes upon miR-203's induction in mouse skin and identified new targets of miR-203. We use two pairs of biological duplicates to perform the microarray analysis from the epidermal samples harvested from K14-rtTA/TRE-miR-203/K14-H2BGFP (DP) and TRE-miR-203/K14-H2BGFP (SP) littermates at P4, 24h after the Dox injection.
Project description:We identify numerous miR-203 in vivo targets that are highly enriched for the promotion of cell cycle and cell division. Importantly, individual targets including p63, Skp2 and Msi2 play distinct roles downstream of miR-203 to regulate the cell cycle and long-term proliferation. Together, our findings reveal rapid and widespread impact of miR-203 on the self-renewal program during the epidermal differentiation and provide mechanistic insights for the potent role of miR-203 where coordinated repression of multiple targets is required for the function of this miRNA. We used microarrays to measure transcriptome changes upon miR-203's induction in mouse skin and identified new targets of miR-203.
Project description:How exercise therapy modulates the host systemic environment to regulate tumor evolution in humans is not known. We performed personalized, multiparametric, longitudinal profiling before, during, and after short-term endurance exercise in 13 patients with solid tumors in a preoperative “window” study.
Project description:Coordinated regulation of the ubiquitin-proteasome system is crucial for the cell to adjust its protein degradation capacity to changing proteolytic requirements. The transcription factor TCF11 has been identified as a regulator for 26S-proteasome formation in human cells to compensate for reduced proteolytic activity. To expand the current knowledge of other UPS-related TCF11 target genes in response to epoxomicin, we performed microarray analyses of cells exposed to epoxomicin and with or without depletion of TCF11. Keywords: siRNA depletion
Project description:Coordinated regulation of the ubiquitin-proteasome system is crucial for the cell to adjust its protein degradation capacity to changing proteolytic requirements. The transcription factor TCF11 has been identified as a regulator for 26S-proteasome formation in human cells to compensate for reduced proteolytic activity. To expand the current knowledge of other UPS-related TCF11 target genes in response to epoxomicin, we performed microarray analyses of cells exposed to epoxomicin and with or without depletion of TCF11. Keywords: siRNA depletion Human Ea.hy926 cells were harvested 24 hours following treatment with 10nM epoxomicin or DMSO as a solvent control and with transfection of control siRNA or TCF11-specific siRNA for RNA extraction and hybridization on Affymetrix microarrays.