The researchers present the first integrative catalogue of 267 cullin–RING substrate receptors, of which 93 are linked to germline disorders.

The most frequent substrate receptor (SR)-related diseases are neurodevelopmental, neuromuscular, and congenital organ/skeletal syndromes.

Disease associations are shaped by substrate context rather than tissue enriched expression.

Pathogenicity arises through altered degron recognition, disrupted complex assembly, dosage imbalance, or ubiquitin–proteasome system-independent functions.

Distinct variants in the same SR can yield divergent phenotypes, reflecting dosage sensitivity and developmental context.

Patient alleles inform diagnosis and therapeutic strategies, positioning SRs as central nodes connecting proteostasis, rare-disease genetics, and targeted protein degradation. sciencenewshighlights ScienceMission https://sciencemission.com/Cullin%E2%80%93RING-receptors

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Priti Agarwal, Ronen Zaidel-Bar et al. define the stage-specific gene expression programs of a leader cell that drives collective tissue invasion during organ development, identifying membrane trafficking as a central regulator of leader cell behavior.

Migration.

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Collective cell invasion underlies organ development, epithelial repair, and cancer metastasis. “Leader cells” remodel ECM, sense guidance cues, reorganize their cytoskeleton, and coordinate follower cells, but the molecular programs enabling these functions remain unclear. Here, we present a stage-specific transcriptomic dataset of the Caenorhabditis elegans gonadal leader cell, the distal tip cell (DTC), which invades basement membrane and guides germ cells to form U-shaped gonadal arms. Comparing invasive larval-stage DTCs with noninvasive adult-stage DTCs defines the molecular signature of an actively invading leader cell in vivo. Our dataset recapitulates known regulators of gonad morphogenesis and reveals numerous uncharacterized genes with potential roles in leader cell activity. Demonstrating dataset utility, we identify vesicular trafficking proteins enriched in invading DTCs and demonstrate their importance for gonad development using endogenous tagging and DTC-specific RNAi. We also catalog diverse DTC-specific knockdown phenotypes. This resource establishes a molecular framework for leader cell activity and a platform to investigate conserved mechanisms of invasive migration.

A new form of in vivo CAR-T therapy kills leukemia, multiple myeloma, and sarcoma in mice, opening the door to a future off-the-shelf cancer treatment without chemotherapy.

For years, one of the most powerful weapons against certain blood cancers, called CAR-T therapy, has required an elaborate process: Doctors extract a patient’s immune cells, ship them to a specialized facility where they’re genetically reprogrammed to fight cancer, then ship them back for infusion into the patient’s bloodstream. This has revolutionized cancer treatment, but the time and expense place it out of reach for thousands of patients.

Now, scientists at UC San Francisco and UC Berkeley have developed a method to precisely reprogram these cancer-fighting cells directly inside the body, potentially eliminating the barriers that have kept this life-saving therapy out of reach for many patients around the world.

https://doi.org/10.1172/jci.insight.

Here, Tobias B. Huber & team use a state-of-the-art, tour de force experimental design to show LSD1 regulates kidney development, and its dysfunction disrupts key kidney cells, leading to cyst formation in mouse and organoid models.

The image shows severe structural changes in the adult mouse kidney with loss of KDM1a. Nephrology.

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⁴Faculty of Biology, Albert Ludwigs University of Freiburg, Freiburg, Germany.

⁵Institute of Medical Bioinformatics and Systems Medicine and.

⁶Institute of Surgical Pathology, Faculty of Medicine, Medical Center — University of Freiburg, Freiburg, Germany.