What is it about?
Our study explores the essential role of the protein DET1 in brain development in both mice and humans. DET1 works with another protein, COP1, to recruit specific transcription factors for tagging by a larger E3 ligase complex. This tagging process, known as polyubiquitination, marks these transcription factors for degradation, thereby regulating the activation and deactivation of other genes. Mice lacking Det1 are not born, while those missing Det1 specifically in neural stem cells exhibit neurological defects and die shortly after birth. We also found a mutation in DET1 linked to lethal developmental defects in humans. This mutation leads to the accumulation of transcription factors, resulting in abnormal gene expression, mitochondrial dysfunction, and increased cell death during neuronal differentiation. Additionally, DET1 plays a crucial role in microglia, helping to limit their neurotoxicity.
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This page is a summary of: Impairment of DET1 causes neurological defects and lethality in mice and humans, Proceedings of the National Academy of Sciences, February 2025, Proceedings of the National Academy of Sciences,
DOI: 10.1073/pnas.2422631122.
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