@article{VollmuthSchlickerGuoetal.2022,
  author    = {Vollmuth, Nadine and Schlicker, Lisa and Guo, Yongxia and Hovhannisyan, Pargev and Janaki-Raman, Sudha and Kurmasheva, Naziia and Schmitz, Werner and Schulze, Almut and Stelzner, Kathrin and Rajeeve, Karthika and Rudel, Thomas},
  title     = {c-Myc plays a key role in IFN-γ-induced persistence of Chlamydia trachomatis},
  series = {eLife},
  volume    = {11},
  journal   = {eLife},
  doi       = {10.7554/eLife.76721},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-301385},
  year      = {2022},
  abstract  = {Chlamydia trachomatis (Ctr) can persist over extended times within their host cell and thereby establish chronic infections. One of the major inducers of chlamydial persistence is interferon-gamma (IFN-γ) released by immune cells as a mechanism of immune defence. IFN-γ activates the catabolic depletion of L-tryptophan (Trp) via indoleamine-2,3-dioxygenase (IDO), resulting in persistent Ctr. Here, we show that IFN-γ induces the downregulation of c-Myc, the key regulator of host cell metabolism, in a STAT1-dependent manner. Expression of c-Myc rescued Ctr from IFN-γ-induced persistence in cell lines and human fallopian tube organoids. Trp concentrations control c-Myc levels most likely via the PI3K-GSK3β axis. Unbiased metabolic analysis revealed that Ctr infection reprograms the host cell tricarboxylic acid (TCA) cycle to support pyrimidine biosynthesis. Addition of TCA cycle intermediates or pyrimidine/purine nucleosides to infected cells rescued Ctr from IFN-γ-induced persistence. Thus, our results challenge the longstanding hypothesis of Trp depletion through IDO as the major mechanism of IFN-γ-induced metabolic immune defence and significantly extends the understanding of the role of IFN-γ as a broad modulator of host cell metabolism.},
  language  = {en}
}
@article{SchwarzLukassenBhandareetal.2022,
  author    = {Schwarz, Jessica Denise and Lukassen, S{\"o}ren and Bhandare, Pranjali and Eing, Lorenz and Snaebj{\"o}rnsson, Marteinn Thor and Garc{\´i}a, Yiliam Cruz and Kisker, Jan Philipp and Schulze, Almut and Wolf, Elmar},
  title     = {The glycolytic enzyme ALDOA and the exon junction complex protein RBM8A are regulators of ribosomal biogenesis},
  series = {Frontiers in Cell and Developmental Biology},
  volume    = {10},
  journal   = {Frontiers in Cell and Developmental Biology},
  issn      = {2296-634X},
  doi       = {10.3389/fcell.2022.954358},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-290875},
  year      = {2022},
  abstract  = {Cellular growth is a fundamental process of life and must be precisely controlled in multicellular organisms. Growth is crucially controlled by the number of functional ribosomes available in cells. The production of new ribosomes depends critically on the activity of RNA polymerase (RNAP) II in addition to the activity of RNAP I and III, which produce ribosomal RNAs. Indeed, the expression of both, ribosomal proteins and proteins required for ribosome assembly (ribosomal biogenesis factors), is considered rate-limiting for ribosome synthesis. Here, we used genetic screening to identify novel transcriptional regulators of cell growth genes by fusing promoters from a ribosomal protein gene (Rpl18) and from a ribosomal biogenesis factor (Fbl) with fluorescent protein genes (RFP, GFP) as reporters. Subsequently, both reporters were stably integrated into immortalized mouse fibroblasts, which were then transduced with a genome-wide sgRNA-CRISPR knockout library. Subsequently, cells with altered reporter activity were isolated by FACS and the causative sgRNAs were identified. Interestingly, we identified two novel regulators of growth genes. Firstly, the exon junction complex protein RBM8A controls transcript levels of the intronless reporters used here. By acute depletion of RBM8A protein using the auxin degron system combined with the genome-wide analysis of nascent transcription, we showed that RBM8A is an important global regulator of ribosomal protein transcripts. Secondly, we unexpectedly observed that the glycolytic enzyme aldolase A (ALDOA) regulates the expression of ribosomal biogenesis factors. Consistent with published observations that a fraction of this protein is located in the nucleus, this may be a mechanism linking transcription of growth genes to metabolic processes and possibly to metabolite availability.},
  language  = {en}
}
@article{LoehrHaertigSchulzeetal.2022,
  author    = {L{\"o}hr, Mario and H{\"a}rtig, Wolfgang and Schulze, Almut and Kroiß, Matthias and Sbiera, Silviu and Lapa, Constantin and Mages, Bianca and Strobel, Sabrina and Hundt, Jennifer Elisabeth and Bohnert, Simone and Kircher, Stefan and Janaki-Raman, Sudha and Monoranu, Camelia-Maria},
  title     = {SOAT1: A suitable target for therapy in high-grade astrocytic glioma?},
  series = {International Journal of Molecular Sciences},
  volume    = {23},
  journal   = {International Journal of Molecular Sciences},
  number    = {7},
  issn      = {1422-0067},
  doi       = {10.3390/ijms23073726},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-284178},
  year      = {2022},
  abstract  = {Targeting molecular alterations as an effective treatment for isocitrate dehydrogenase-wildtype glioblastoma (GBM) patients has not yet been established. Sterol-O-Acyl Transferase 1 (SOAT1), a key enzyme in the conversion of endoplasmic reticulum cholesterol to esters for storage in lipid droplets (LD), serves as a target for the orphan drug mitotane to treat adrenocortical carcinoma. Inhibition of SOAT1 also suppresses GBM growth. Here, we refined SOAT1-expression in GBM and IDH-mutant astrocytoma, CNS WHO grade 4 (HGA), and assessed the distribution of LD in these tumors. Twenty-seven GBM and three HGA specimens were evaluated by multiple GFAP, Iba1, IDH1 R132H, and SOAT1 immunofluorescence labeling as well as Oil Red O staining. To a small extent SOAT1 was expressed by tumor cells in both tumor entities. In contrast, strong expression was observed in glioma-associated macrophages. Triple immunofluorescence labeling revealed, for the first time, evidence for SOAT1 colocalization with Iba1 and IDH1 R132H, respectively. Furthermore, a notable difference in the amount of LD between GBM and HGA was observed. Therefore, SOAT1 suppression might be a therapeutic option to target GBM and HGA growth and invasiveness. In addition, the high expression in cells related to neuroinflammation could be beneficial for a concomitant suppression of protumoral microglia/macrophages.},
  language  = {en}
}