PMA-induced GCMa phosphorylation stimulates its transcriptional activity and degradation

Glial cells missing Drosophila homolog a (GCMa) is a member of the GCM transcription factor family and plays critical roles in trophoblast differentiation and placental functions. It is well established that the cyclic AMP (cAMP)-dependent pathway induces the expression and transcriptional activity...

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Bibliographic Details
Published in:Biomedical Research 2012, Vol.33(4), pp.217-224
Main Authors: Yasui, Yuko, Miyazawa, Daisuke, Ueda, Hiroshi, Sato, Katsuya, Kitade, Yukio, Yamada, Kazuyo
Format: Article
Language:English
Subjects:
Cell Differentiation
Enzyme-Linked Immunosorbent Assay
HEK293 Cells
Humans
MAP Kinase Signaling System
Nuclear Proteins - genetics
Nuclear Proteins - metabolism
Phosphorylation
Protein Kinase C - metabolism
Protein Stability
Proteolysis
Serine - metabolism
Tetradecanoylphorbol Acetate - analogs & derivatives
Tetradecanoylphorbol Acetate - pharmacology
Transcription Factors - genetics
Transcription Factors - metabolism
Transcriptional Activation
Trophoblasts - metabolism
Ubiquitination
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Summary:Glial cells missing Drosophila homolog a (GCMa) is a member of the GCM transcription factor family and plays critical roles in trophoblast differentiation and placental functions. It is well established that the cyclic AMP (cAMP)-dependent pathway induces the expression and transcriptional activity of GCMa by regulating post-translational modifications of GCMa, which results in enhancement of trophoblast differentiation. We previously observed that phorbol 12-myristate 13-acetate (PMA) stimulates phosphorylation of GCMa on serines 328, 378 and 383 through the protein kinase C (PKC)- and mitogen-activated protein kinase kinase (MEK)/extracellular signalregulated kinase (ERK)-dependent pathway, which decreases the protein stability of GCMa. Here we report that PMA increases the ubiquitination level of GCMa, dependent on the phosphorylation of GCMa on serines 328, 378 and 383. We found that this phosphorylation also stimulates the transcriptional activity of GCMa. Our data indicate that the PMA-induced PKC- and MEK/ERKdependent pathway enhances the degradation as well as the transcriptional activity of GCMa. We also examined the impact of this signaling pathway on trophoblasts and the results suggest that the PKC- and MEK/ERK-dependent pathway is involved in the regulation of trophoblast differentiation.
ISSN:0388-6107
1880-313X
DOI:10.2220/biomedres.33.217