Regulation of GCM1 Stability by Protein Dephosphorylation
Date Issued
2009
Date
2009
Author(s)
Lin, Fang-Yu
Abstract
Human GCM1 (Glial cell missing homolog 1) is a placenta-specific transcription factor, which regulates expression of syncytin, a fusogenic membrane protein, and controls the formation of syncytiotrophoblast layer essential for nutrient and gas exchange. In previous studies, we have demonstrated that GCM1 activity can be regulated by different post-translational modifications, including phosphoryaltion, ubiquitination, sumoylation and acetylation. Very recently, it has further been demonstrated that activation of GSK-3β by hypoxia leads to GCM1 phosphorylation on Ser322, which in turn recruits the F-box protein FBW2 to trigger GCM1 ubiquitination and degradation. In this report, we further identify a dual-specificity protein phosphatase termed GIP1 (GCM1-interacting protein 1), which regulates GCM1 dephosphorylation on Ser322 leading to reduction in GCM1 ubiquitination, and therefore increase in GCM1 stability and transcriptional activity. Together with our previous findings, GCM1 protein stability is reciprocally regulated by GSK-3β and GIP1, which may be critical for regulation of trophoblastic fusion and differentiation of syncytiotrophoblast layer.
Subjects
Protein dephosphorylation
stability
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