Plakoglobin is O-glycosylated close to the N-terminal destruction box.
Plakoglobin provides a key linkage in protein chains that connect desmosomal and classical cadherins to the cytoskeleton. It is also present in a significant cytosolic pool that has the capacity to impact on canonical Wnt signaling by competing for interaction with partner proteins of beta-catenin. The closely related protein, beta-catenin, is rapidly targeted for proteasomal degradation by phosphorylation of a "destruction box" within the N-terminal domain. Inhibition of this process forms the basis of Wnt signaling. This destruction box is also found in the N-terminal domain of plakoglobin. We report that plakoglobin is modified by the addition of O-GlcNAc at a single site in close proximity to the destruction box. O-GlcNAc modification has been proposed to counteract phosphorylation, provide protection from proteasomal degradation, mediate signal transduction, silence transcription, and regulate multimolecular protein assembly. This finding has potential implications for understanding the roles of plakoglobin.
Hatsell
Sarah
S
Department of Cell Biology, New York University Medical School, New York, New York 10016, USA.
Medina
Lillian
L
Merola
Joe
J
Haltiwanger
Robert
R
Cowin
Pamela
P
D000595:Amino Acid Sequence; D001483:Base Sequence; D003598:Cytoskeletal Proteins / Q000737:chemistry* / Q000502:physiology; D051180:Desmoplakins; D038362:Glycogen Synthase Kinase 3 / Q000737:chemistry; D000071679:Glycogen Synthase Kinase 3 beta; D006031:Glycosylation; D006801:Humans; D008969:Molecular Sequence Data; D015534:Trans-Activators / Q000737:chemistry; D051176:beta Catenin; D051185:gamma Catenin
C495270:CTNNB1 protein, human; D003598:Cytoskeletal Proteins; D051180:Desmoplakins; D015534:Trans-Activators; D051176:beta Catenin; D051185:gamma Catenin; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3