Publications by authors named "M Altelaar"
Intestinal stem cells (ISCs) face the challenge of integrating metabolic demands with unique regenerative functions. Studies have shown an intricate interplay between metabolism and stem cell capacity; however, it is still not understood how this process is regulated. Combining ribosome profiling and CRISPR screening in intestinal organoids, we identify the nascent polypeptide-associated complex (NAC) as a key mediator of this process.
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- The study explores how the PD-1 immune checkpoint protein is regulated on CD8 T cells, aiming to find ways to lower its abundance without hindering T cell activation, which is crucial for effective cancer therapy.
- Researchers conducted a CRISPR-Cas9 screen on murine CD8 T cells to identify genes impacting PD-1 levels, discovering that inhibiting the TMED protein family, especially TMED10, could reduce PD-1 on the cell surface and enhance T cell function.
- The findings highlight a new regulatory mechanism for PD-1 and suggest that targeting TMED could be a promising therapeutic strategy to improve T cell responses in cancer treatment, as indicated by correlations in mouse models and patient survival data.
Inflammatory cytokines are pivotal to immune responses. Upon cytokine exposure, cells enter an "alert state" that enhances their visibility to the immune system. Here, we identified an alert-state subpopulation of ribosomes defined by the presence of the P-stalk.
View Article and Find Full Text PDFThe Fanconi anemia (FA) repair pathway governs repair of highly genotoxic DNA interstrand crosslinks (ICLs) and relies on translesion synthesis (TLS). TLS is facilitated by REV1 or site-specific monoubiquitination of proliferating cell nuclear antigen (PCNA) (PCNA-Ub) at lysine 164 (K164). A but not mutation renders mammals hypersensitive to ICLs.
View Article and Find Full Text PDFLocal mRNA translation in axons is critical for the spatiotemporal regulation of the axonal proteome. A wide variety of mRNAs are localized and translated in axons; however, how protein synthesis is regulated at specific subcellular sites in axons remains unclear. Here, we establish that the axonal endoplasmic reticulum (ER) supports axonal translation in developing rat hippocampal cultured neurons.
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