Yifat oren biography samples
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Multiplex genomic tagging of mammalian ATG8s to study autophagy
Abstract
Atg8 proteins play a crucial role in autophagy. There is a single Atg8 isoform in yeast, while mammals have up to seven homologs categorized into LC3s and GABARAPs. The GABARAP subfamily consists of GABARAP, GABARAPL1, and GABARAPL2/GATE16, implicated in various stages along the pathway. However, the intricacies among GABARAP proteins are complex and require a more precise delineation. Here, we introduce a new cellular platform to study autophagy using CRISPR/Cas9-mediated tagging of endogenous genes of the GABARAP subfamily with different fluorescent proteins. This platform allows robust examination of autophagy by flow cytometry of cell populations and monitoring of GABARAP homologs at single-cell resolution using fluorescence microscopy. Strikingly, the simultaneous labeling of the different endogenous GABARAPs allows the identification and isolation of autophagosomes differentially marked by these protein
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Abstract
One-third of monogenic inherited diseases result from premature termination codons (PTCs). Readthrough of in-frame PTCs enables synthesis of full-length functional proteins. However, extended variability in the response to readthrough treatment is found among patients, which correlates with the level of nonsense transcripts. Here, we aimed to reveal cellular pathways affecting this inter-patient variability. We show that activation of the unfolded protein response (UPR) governs the response to readthrough treatment by regulating the levels of transcripts carrying PTCs. Quantitative proteomic analyses showed substantial differences in UPR activation between patients carrying PTCs, correlating with their response. We further found a significant inverse correlation between the UPR and nonsense-mediated mRNA decay (NMD), suggesting a feedback loop between these homeostatic pathways. We uncovered and characterized the mechanism underlying this NMD-UPR feedback loop, which augme
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Fifteen years of APC/cyclosome: a short and impressive biography
78 Biochemical kultur Transactions () Volume 38, part 1 Fifteen years of APC/cyclosome: a short and impressive biography Kobi J. Simpson-Lavy, Yifat S. Oren, Oren Feine, Julia Sajman, Tammy Listovsky and Michael Brandeis1 Department of Genetics, The Silberman Institute of Life Sciences, Hebrew University of Jerusalem, Jerusalem , Israel Abstract The APC/C (anaphase-promoting complex/cyclosome) discovered exactly 15 years ago by Avram Heshko and Marc Kirschner is bygd far the most complex ubiquitin ligase discovered so far. The APC/C fryst vatten composed of roughly a dozen subunits and measures a massive MDa. This huge complex, as well as its multiple modes of regulation, boasts impressive evolutionary conservation. One of its most puzzling features is its split personality: regulation of mitotic exit events on the one hand, and its ongoing activity during G1 -phase, G0 -phase and in terminally differentiated cells. The present