ArticleCell death & disease2024
CUL4B mutations impair human cortical neurogenesis through PP2A-dependent inhibition of AKT and ERK.
Article in Cell death & disease, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers, 1 of them a synthesis that pooled it.
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Who cites it
12 citing papers in PubMed, 1 synthesis or guideline pooled it, 8 citations in OpenAlex.
- Mapping the Cerebral Organoid Landscape: A Systematic Review of Preclinical 3D Models in Neuroscience.Advanced healthcare materials · 2026Pooled it
- Review
- Brain organoids and genome editing: A new era in understanding human brain development and disorders.Neural regeneration research · 2026Article
- Decreased PP2A expression and activity represent a therapeutic target for plexiform neurofibroma.Acta neuropathologica communications · 2026Article
- OR2T6 modulates autophagy through the PPP3CA-mediated pathways to suppress gastric cancer.Cell death and differentiation · 2026Article
- Cul5: immune cell function and therapeutic potential.Frontiers in immunology · 2026Review
- CUL4B promotes hepatocellular carcinoma progression and oxaliplatin resistance by facilitating FUS degradation.Cell death & disease · 2025Article
- Fetuin B Is Related to Cytokine/Chemokine and Insulin Signaling in Adipose Tissue and Plasma in Humans.The Journal of clinical endocrinology and metabolism · 2025Article
- GABA transporter 1 is a promising drug target for CUL4B mutation-associated epilepsy.Acta pharmacologica Sinica · 2025Article
- An Insight into Differentially Expressed Genes and MicroRNAs in the Pituitary Glands of the Two Estrous Phases of Sheep with DifferentAnimals : an open access journal from MDPI · 2025Article
- CUL4B protects kidneys from acute injury by restraining p53/PAI-1 signaling.Cell death & disease · 2024Article
- The X-linked intellectual disability gene CUL4B is critical for memory and synaptic function.Acta neuropathologica communications · 2024Article
Corrections and comments
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
Abstract
Mutation in CUL4B gene is one of the most common causes for X-linked intellectual disability (XLID). CUL4B is the scaffold protein in CUL4B-RING ubiquitin ligase (CRL4B) complex. While the roles of CUL4B in cancer progression and some developmental processes like adipogenesis, osteogenesis, and spermatogenesis have been studied, the mechanisms underlying the neurological disorders in patients with CUL4B mutations are poorly understood. Here, using 2D neuronal culture and cerebral organoids generated from the patient-derived induced pluripotent stem cells and their isogenic controls, we demonstrate that CUL4B is required to prevent premature cell cycle exit and precocious neuronal differentiation of neural progenitor cells. Moreover, loss-of-function mutations of CUL4B lead to increased synapse formation and enhanced neuronal excitability. Mechanistically, CRL4B complex represses transcription of PPP2R2B and PPP2R2C genes, which encode two isoforms of the regulatory subunit of protein phosphatase 2 A (PP2A) complex, through catalyzing monoubiquitination of H2AK119 in their promoter regions. CUL4B mutations result in upregulated PP2A activity, which causes inhibition of AKT and ERK, leading to premature cell cycle exit. Activation of AKT and ERK or inhibition of PP2A activity in CUL4B mutant organoids rescues the neurogenesis defect. Our work unveils an essential role of CUL4B in human cortical development.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.