ArticleMolecular and cellular biology2005
Stimulation of GCMa transcriptional activity by cyclic AMP/protein kinase A signaling is attributed to CBP-mediated acetylation of GCMa.
Article in Molecular and cellular biology, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 94 citations in OpenAlex.
- The regulatory network of Mfsd2a in cerebral ischemia: a novel time-targeted intervention framework.Molecular biology reports · 2026Review
- aPKC-ζ III promotes trophoblast fusion by altering Par-3 interactions with Hippo signaling kinase LATS1.Stem cell reports · 2026Article
- The influence of cell-cell fusion on cancer heterogeneity and its promise for targeted treatments.Cellular oncology (Dordrecht, Netherlands) · 2026Review
- Regulation of placental development and function by ubiquitination.Molecular medicine (Cambridge, Mass.) · 2025Review
- Molecular mechanisms of syncytin-1 in tumors and placental development related diseases.Discover oncology · 2023Review
- Accessing the human trophoblast stem cell state from pluripotent and somatic cells.Cellular and molecular life sciences : CMLS · 2022Review
- How trophoblasts fuse: an in-depth look into placental syncytiotrophoblast formation.Cellular and molecular life sciences : CMLS · 2022Review
- An integrated atlas of human placental development delineates essential regulators of trophoblast stem cells.Development (Cambridge, England) · 2022Article
- Functional antagonism between ΔNp63α and GCM1 regulates human trophoblast stemness and differentiation.Nature communications · 2022Article
- Structure-based prediction of HDAC6 substrates validated by enzymatic assay reveals determinants of promiscuity and detects new potential substrates.Scientific reports · 2022Article
- Cell Fusion-Related Proteins and Signaling Pathways, and Their Roles in the Development and Progression of Cancer.Frontiers in cell and developmental biology · 2021Review
- New insights into the regulation of placental growth factor gene expression by the transcription factors GCM1 and DLX3 in human placenta.The Journal of biological chemistry · 2018Article
- p45 NF-E2 regulates syncytiotrophoblast differentiation by post-translational GCM1 modifications in human intrauterine growth restriction.Cell death & disease · 2017Article
- GATA3 inhibits GCM1 activity and trophoblast cell invasion.Scientific reports · 2016Article
- A Positive Feedback Loop between Glial Cells Missing 1 and Human Chorionic Gonadotropin (hCG) Regulates Placental hCGβ Expression and Cell Differentiation.Molecular and cellular biology · 2016Article
- A CRE/AP-1-like motif is essential for induced syncytin-2 expression and fusion in human trophoblast-like model.PloS one · 2015Article
- Expression of flotillins in the human placenta: potential implications for placental transcytosis.Histochemistry and cell biology · 2013Article
- Reduced syncytin-1 expression levels in placental syndromes correlates with epigenetic hypermethylation of the ERVW-1 promoter region.PloS one · 2013Article
- High-temperature requirement protein A4 (HtrA4) suppresses the fusogenic activity of syncytin-1 and promotes trophoblast invasion.Molecular and cellular biology · 2012Article
- The cis-regulatory code of Hox function in Drosophila.The EMBO journal · 2012Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
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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