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Transcription factors regulated by cAMP in smooth muscle of the myometrium at human parturition

Research output: Contribution to journalReview articlepeer-review

Jonathan K.H. Li, Pei F. Lai, Rachel M. Tribe, Mark R. Johnson

Original languageEnglish
Pages (from-to)997-1011
Number of pages15
JournalBiochemical Society Transactions
Issue number2
PublishedApr 2021

Bibliographical note

Funding Information: PhD studentship for JKHL is funded by Borne (registered charity number 1167073) with assistance from the Robert McAlpine Foundation (registered charity number 226646). The academic research activities of PFL and MRJ are funded by Borne; RMT is funded by HEFCE (King’s College London), with current myometrium-related research funded by Tommy’s baby charity (registered charity number 1060508) and Borne. Publisher Copyright: © 2021 Portland Press Ltd. All rights reserved. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.

King's Authors


Cyclic adenosine monophosphate (cAMP) contributes to maintenance of a quiescent (relaxed) state in the myometrium (i.e. uterine smooth muscle) during pregnancy, which most commonly has been attributed to activation of protein kinase A (PKA). PKAmediated phosphorylation of cytosolic contractile apparatus components in myometrial smooth muscle cells (mSMCs) are known to promote relaxation. Additionally, PKA also regulates nuclear transcription factor (TF) activity to control expression of genes important to the labour process; these are mostly involved in actin-myosin interactions, cell-tocell connectivity and inflammation, all of which influence mSMC transition from a quiescent to a contractile (pro-labour) phenotype. This review focuses on the evidence that cAMP modulates the activity of TFs linked to pro-labour gene expression, predominantly cAMP response element (CRE) binding TFs, nuclear factor κB (NF-κB), activator protein 1 (AP-1) family and progesterone receptors (PRs). This review also considers the more recently described exchange protein directly activated by cAMP (EPAC) that may oppose the pro-quiescent effects of PKA, as well as explores findings from other cell types that have the potential to be of novel relevance to cAMP action on TF function in the myometrium.

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