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

TY - JOUR

T1 - MID1, mutated in Opitz syndrome, encodes an ubiquitin ligase that targets phosphatase 2A for degradation

AU - Trockenbacher, Alexander

AU - Suckow, Vanessa

AU - Foerster, John

AU - Winter, Jennifer

AU - Krauss, Sybille

AU - Ropers, Hans-Hilger

AU - Schneider, Rainer

AU - Schweiger, Susann

N1 - dc.publisher: Nature.com

PY - 2001

Y1 - 2001

N2 - 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.

AB - 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.

U2 - 10.1038/ng762

DO - 10.1038/ng762

M3 - Article

C2 - 11685209

SN - 1061-4036

VL - 29

SP - 287

EP - 294

JO - Nature Genetics

JF - Nature Genetics

IS - 3

ER -