MID1, mutated in Opitz syndrome, encodes an ubiquitin ligase that targets phosphatase 2A for degradation

Alexander Trockenbacher, Vanessa Suckow, John Foerster, Jennifer Winter, Sybille Krauss, Hans-Hilger Ropers, Rainer Schneider, Susann Schweiger

    Research output: Contribution to journalArticlepeer-review

    214 Citations (Scopus)

    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 4 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.
    Original languageEnglish
    Pages (from-to)287-294
    Number of pages8
    JournalNature Genetics
    Volume29
    Issue number3
    DOIs
    Publication statusPublished - 2001

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