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- Title
MID1, mutated in Opitz syndrome, encodes an ubiquitin ligase that targets phosphatase 2A for degradation.
- Authors
Trockenbacher, Alexander; Suckow, Vanessa; Foerster, John; Winter, Jennifer; Krauß, Sybille; Ropers, Hans-Hilger; Schneider, Rainer; Schweiger, Susann
- Abstract
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 α4 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.
- Subjects
UBIQUITIN; PHOSPHATASES; BIODEGRADATION; GENETIC mutation
- Publication
Nature Genetics, 2001, Vol 29, Issue 3, p287
- ISSN
1061-4036
- Publication type
Article
- DOI
10.1038/ng762