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Stimulation of GCMa transcriptional activity by cyclic AMP/protein kinase A signaling is attributed to CBP-mediated acetylation of GCMa.

Publication ,  Journal Article
Chang, C-W; Chuang, H-C; Yu, C; Yao, T-P; Chen, H
Published in: Mol Cell Biol
October 2005

Human GCMa is a zinc-containing transcription factor primarily expressed in placenta. GCMa regulates expression of syncytin gene, which encodes for a placenta-specific membrane protein that mediates trophoblastic fusion and the formation of syncytiotrophoblast layer required for efficient fetal-maternal exchange of nutrients and oxygen. The adenylate cyclase activator, forskolin, stimulates syncytin gene expression and cell fusion in cultured placental cells. Here we present evidence that cyclic AMP (cAMP) signaling pathway activates the syncytin gene expression by regulating GCMa activity. We found that forskolin and protein kinase A (PKA) enhances GCMa-mediated transcriptional activation. Furthermore, PKA treatment stimulates the association of GCMa with CBP and increases GCMa acetylation. CBP primarily acetylates GCMa at lysine367, lysine406, and lysine409 in the transactivation domain (TAD). We found that acetylation of these residues is required to protect GCMa from ubiquitination and increases the TAD stability with a concomitant increase in transcriptional activity, supporting the importance of acetylation in PKA-dependent GCMa activation. Our results reveal a novel regulation of GCMa activity by cAMP-dependent protein acetylation and provide a molecular mechanism by which cAMP signaling regulates trophoblastic fusion.

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Published In

Mol Cell Biol

DOI

ISSN

0270-7306

Publication Date

October 2005

Volume

25

Issue

19

Start / End Page

8401 / 8414

Location

United States

Related Subject Headings

  • Zinc
  • Up-Regulation
  • Ubiquitin
  • Trophoblasts
  • Transfection
  • Transcriptional Activation
  • Transcription, Genetic
  • Transcription Factors
  • Time Factors
  • Signal Transduction
 

Citation

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Chang, C.-W., Chuang, H.-C., Yu, C., Yao, T.-P., & Chen, H. (2005). Stimulation of GCMa transcriptional activity by cyclic AMP/protein kinase A signaling is attributed to CBP-mediated acetylation of GCMa. Mol Cell Biol, 25(19), 8401–8414. https://doi.org/10.1128/MCB.25.19.8401-8414.2005
Chang, Ching-Wen, Hsiao-Ching Chuang, Chenchou Yu, Tso-Pang Yao, and Hungwen Chen. “Stimulation of GCMa transcriptional activity by cyclic AMP/protein kinase A signaling is attributed to CBP-mediated acetylation of GCMa.Mol Cell Biol 25, no. 19 (October 2005): 8401–14. https://doi.org/10.1128/MCB.25.19.8401-8414.2005.
Chang, Ching-Wen, et al. “Stimulation of GCMa transcriptional activity by cyclic AMP/protein kinase A signaling is attributed to CBP-mediated acetylation of GCMa.Mol Cell Biol, vol. 25, no. 19, Oct. 2005, pp. 8401–14. Pubmed, doi:10.1128/MCB.25.19.8401-8414.2005.

Published In

Mol Cell Biol

DOI

ISSN

0270-7306

Publication Date

October 2005

Volume

25

Issue

19

Start / End Page

8401 / 8414

Location

United States

Related Subject Headings

  • Zinc
  • Up-Regulation
  • Ubiquitin
  • Trophoblasts
  • Transfection
  • Transcriptional Activation
  • Transcription, Genetic
  • Transcription Factors
  • Time Factors
  • Signal Transduction