A Survey on the Expression of the Ubiquitin Proteasome System Components HECT- and RBR-E3 Ubiquitin Ligases and E2 Ubiquitin-Conjugating and E1 Ubiquitin-Activating Enzymes during Human Brain Development.

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  • Additional Information
    • Source:
      Publisher: MDPI Country of Publication: Switzerland NLM ID: 101092791 Publication Model: Electronic Cited Medium: Internet ISSN: 1422-0067 (Electronic) Linking ISSN: 14220067 NLM ISO Abbreviation: Int J Mol Sci Subsets: MEDLINE
    • Publication Information:
      Original Publication: Basel, Switzerland : MDPI, [2000-
    • Subject Terms:
      Ubiquitin-Protein Ligases*/genetics ; Ubiquitin-Protein Ligases*/metabolism ; Ubiquitin-Activating Enzymes*/metabolism; Humans ; Ubiquitin/genetics ; Ubiquitin/metabolism ; Proteasome Endopeptidase Complex/metabolism ; Ubiquitination ; Ubiquitin-Conjugating Enzymes/genetics ; Ubiquitin-Conjugating Enzymes/metabolism ; Brain/metabolism
    • Abstract:
      Human brain development involves a tightly regulated sequence of events that starts shortly after conception and continues up to adolescence. Before birth, neurogenesis occurs, implying an extensive differentiation process, sustained by changes in the gene expression profile alongside proteome remodeling, regulated by the ubiquitin proteasome system (UPS) and autophagy. The latter processes rely on the selective tagging with ubiquitin of the proteins that must be disposed of. E3 ubiquitin ligases accomplish the selective recognition of the target proteins. At the late stage of neurogenesis, the brain starts to take shape, and neurons migrate to their designated locations. After birth, neuronal myelination occurs, and, in parallel, neurons form connections among each other throughout the synaptogenesis process. Due to the malfunctioning of UPS components, aberrant brain development at the very early stages leads to neurodevelopmental disorders. Through deep data mining and analysis and by taking advantage of machine learning-based models, we mapped the transcriptomic profile of the genes encoding HECT- and ring-between-ring (RBR)-E3 ubiquitin ligases as well as E2 ubiquitin-conjugating and E1 ubiquitin-activating enzymes during human brain development, from early post-conception to adulthood. The inquiry outcomes unveiled some implications for neurodevelopment-related disorders.
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    • Contributed Indexing:
      Keywords: brain development; machine learning and model classification; neurodegenerative disorders; neurodevelopmental disorders; proteome remodeling; ubiquitin proteasome system (UPS)
    • Accession Number:
      EC 2.3.2.27 (Ubiquitin-Protein Ligases)
      EC 6.2.1.45 (Ubiquitin-Activating Enzymes)
      0 (Ubiquitin)
      EC 3.4.25.1 (Proteasome Endopeptidase Complex)
      EC 2.3.2.23 (Ubiquitin-Conjugating Enzymes)
    • Publication Date:
      Date Created: 20240224 Date Completed: 20240226 Latest Revision: 20240227
    • Publication Date:
      20240227
    • Accession Number:
      PMC10889685
    • Accession Number:
      10.3390/ijms25042361
    • Accession Number:
      38397039