MID1, mutated in Opitz syndrome, encodes an ubiquitin ligase that targets phosphatase 2A for degradation.
The gene MID1, the mutation of which causes X-linked Opitz G/BBB syndrome (OS, MIM 300000), encodes a microtubule-associated protein (MAP). We show that mutation of MID1 leads to a marked accumulation of the catalytic subunit of protein phosphatase 2A (PP2Ac), a central cellular regulator. PP2Ac accumulation is caused by an ... impairment of a newly identified E3 ubiquitin ligase activity of the MID1 protein that normally targets PP2Ac for degradation through binding to its alpha4 regulatory subunit in an embryonic fibroblast line derived from a fetus with OS. Elevated PP2Ac causes hypophosphorylation of MAPs, a pathological mechanism that is consistent with the OS phenotype.
Mesh Terms:
Animals, Antigen-Antibody Complex, Binding Sites, Blotting, Western, COS Cells, Fibroblasts, Fluorescent Antibody Technique, Humans, Ligases, Microtubule Proteins, Microtubule-Associated Proteins, Microtubules, Models, Biological, Mutation, Nuclear Proteins, Phosphoprotein Phosphatases, Phosphorylation, Polyubiquitin, Precipitin Tests, Protein Binding, Protein Phosphatase 2, Protein Subunits, Substrate Specificity, Syndrome, Transcription Factors, Two-Hybrid System Techniques, Ubiquitin, Ubiquitin-Protein Ligases, Up-Regulation
Animals, Antigen-Antibody Complex, Binding Sites, Blotting, Western, COS Cells, Fibroblasts, Fluorescent Antibody Technique, Humans, Ligases, Microtubule Proteins, Microtubule-Associated Proteins, Microtubules, Models, Biological, Mutation, Nuclear Proteins, Phosphoprotein Phosphatases, Phosphorylation, Polyubiquitin, Precipitin Tests, Protein Binding, Protein Phosphatase 2, Protein Subunits, Substrate Specificity, Syndrome, Transcription Factors, Two-Hybrid System Techniques, Ubiquitin, Ubiquitin-Protein Ligases, Up-Regulation
Nat. Genet.
Date: Nov. 01, 2001
PubMed ID: 11685209
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