ArticleCell communication and signaling : CCS2014
Internal translation of the connexin 43 transcript.
Article in Cell communication and signaling : CCS, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers, 1 of them a synthesis that pooled it.
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Who cites it
59 citing papers in PubMed, 1 synthesis or guideline pooled it, 85 citations in OpenAlex.
- Mammalian Polycistronic mRNAs and Disease.Trends in genetics : TIG · 2017Pooled it
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- Involvement of connexin 43 in myocardial ischemia-reperfusion injury.Cell and tissue research · 2025Review
- Translational Control in Cardiac Pathophysiology and Therapeutic Development: When mRNA Meets the Heart.International journal of molecular sciences · 2025Review
- Left Ventricular Unloading With Assist Device Implantation Increases GJA1-20k Expression in Patients With Arrhythmogenic Cardiomyopathy.Circulation. Heart failure · 2025Article
- Connexin46 in the nucleus of cancer cells: a possible role as transcription modulator.Cell communication and signaling : CCS · 2025Article
- A truncated isoform of Connexin43 caps actin to organize forward delivery of full-length Connexin43.The Journal of cell biology · 2025Article
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- Connexin 43 regulates intercellular mitochondrial transfer from human mesenchymal stromal cells to chondrocytes.Stem cell research & therapy · 2024Article
- Casein Kinase 1 Phosphomimetic Mutations Negatively Impact Connexin-43 Gap Junctions in Human Pluripotent Stem Cell-Derived Cardiomyocytes.Biomolecules · 2024Article
- Connexins in Cancer, the Possible Role of Connexin46 as a Cancer Stem Cell-Determining Protein.Biomolecules · 2023Review
- The human discs large protein 1 interacts with and maintains connexin 43 at the plasma membrane in keratinocytes.Journal of cell science · 2023Article
- Aberrant TIMP-1 overexpression in tumor-associated fibroblasts drives tumor progression through CD63 in lung adenocarcinoma.Matrix biology : journal of the International Society for Matrix Biology · 2022Article
- Review
- Connexin 43 in Mitochondria: What Do We Really Know About Its Function?Frontiers in physiology · 2022Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundConnexin 43 (Cx43), the most widely expressed gap junction protein, is associated with a number of physiological and pathological conditions. Many functions of Cx43 have been shown to be independent of gap junction formation and only require the expression of Cx43 C-terminal fragments. Recent evidence demonstrated that naturally occurring C-terminal isoforms can be generated via internal translation.
findingsHere, we confirm that C-terminal domains of Cx43, particularly the major 20-kDa isoform, can be independently generated and regulated by internal translation of the same single GJA1 gene transcript that encodes full-length Cx43. Through direct RNA transfection experiments, we provide evidence that internal translation is not due to a bona fide cap-independent IRES-mediated mechanism, as upstream ribosomal scanning or translation is required. In addition to the mTOR pathway, we show for the first time, using both inhibitors and cells from knockout mice, that the Mnk1/2 pathway regulates the translation of the main 20-kDa isoform.
conclusionsInternal translation of the Cx43 transcript occurs but is not cap-independent and requires translation upstream of the internal start codon. In addition to the PI3K/AKT/mTOR pathway, the major 20-kDa isoform is regulated by the Mnk1/2 pathway. Our results have major implications for past and future studies describing gap junction-independent functions of Cx43 in cancer and other pathological conditions. This study provides further clues to the signalling pathways that regulate internal mRNA translation, an emerging mechanism that allows for increased protein diversity and functional complexity from a single mRNA transcript.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.