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Fabian, Z.

Publications and source records attributed to Fabian, Z..

2 recordsLinked to original sources

ProPicker: Promptable Segmentation for Particle Picking in CryogenicElectron Tomography

Cryogenic electron tomography (cryo-ET) produces detailed 3D images (tomograms) of cellular environments. A key step in cryo-ET data analysis is detecting all instances of a specific particle across tomograms (particle picking). This is a challenging object detection task due to strong noise, artefacts, and the crowded cellular context. Here, we propose ProPicker, a pretrained, promptable 3D segmentation model that enables a flexible and data-efficient particle picking workflow. By specifying a prompt, ProPicker is conditioned to detect a particle of interest and can then be used directly or can be fine-tuned to a particle-specific picker for improved accuracy. Experiments on simulated and real-world tomograms show that, using a single prompt, ProPicker achieves performance close to or on par with state-of-the-art methods while being up to an order of magnitude faster. Moreover, ProPicker can detect particles not seen during training. Fine-tuning ProPicker outperforms state-of-the-art particle-specific pickers if limited training data is available.

bioinformatics↗

Profiling ubiquitin signaling with UBIMAX reveals DNA damage- and SCFβTRCP-dependent ubiquitylation of the actin-organizing protein Dbn1

Ubiquitin widely modifies proteins, thereby regulating most cellular functions. The complexity of ubiquitin signalling necessitates unbiased methods enabling global detection of dynamic protein ubiquitylation. Here, we describe UBIMAX (UBiquitin target Identification by Mass spectrometry in Xenopus egg extracts), which enriches ubiquitin-conjugated proteins and quantifies regulation of protein ubiquitylation under precise and adaptable conditions. We benchmark UBIMAX by investigating DNA double-strand break-responsive ubiquitylation events, identifying previously known targets and revealing the actin-organising protein Dbn1 as a novel major target of DNA damage-induced ubiquitylation. We find that Dbn1 is targeted for proteasomal degradation by the SCF{beta}-Trcp1 ubiquitin ligase, in a conserved mechanism driven by ATM-mediated phosphorylation of a previously uncharacterized {beta}-Trcp1 degron containing an SQ motif. We further show that this degron is sufficient to induce DNA-damage dependent protein degradation of a model substrate. Collectively, we demonstrate UBIMAXs ability to identify novel targets of stimulus-regulated ubiquitylation and reveal an SCF{beta}-Trcp1-mediated ubiquitylation mechanism controlled directly by the apical DNA damage response kinases.

molecular biology↗