ArticlePloS one2011
Complex SUMO-1 regulation of cardiac transcription factor Nkx2-5.
Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 39 citations in OpenAlex.
- UBA2: the gatekeeper of the sumoylation pathway and its multifaceted roles in human diseases and therapeutic prospects.Clinical and experimental medicine · 2026Review
- Case Report: A newFrontiers in medicine · 2026Article
- Exome Sequencing to Identify Novel Susceptibility Genes for Nonsyndromic Split-Hand/Ft Malformation: A Report From the National Birth Defects Prevention Study.Birth defects research · 2025Article
- Epigenetic Regulation of Mammalian Cardiomyocyte Development.Epigenomes · 2024Review
- A novel frameshift variant in UBA2 causing split-hand/foot malformations in a Pakistani family.Human genome variation · 2023Article
- Targeting Epigenetic Regulation of Cardiomyocytes through Development for Therapeutic Cardiac Regeneration after Heart Failure.International journal of molecular sciences · 2022Review
- SUMOylation Potentiates ZIC Protein Activity to Influence Murine Neural Crest Cell Specification.International journal of molecular sciences · 2021Article
- UBA2 variants underlie a recognizable syndrome with variable aplasia cutis congenita and ectrodactyly.Genetics in medicine : official journal of the American College of Medical Genetics · 2021Article
- The role of SUMOylation during development.Biochemical Society transactions · 2020Review
- Comprehensive clinical and molecular studies in split-hand/foot malformation: identification of two plausible candidate genes (LRP6 and UBA2).European journal of human genetics : EJHG · 2019Article
- Elk1 affects katanin and spastin proteins via differential transcriptional and post-transcriptional regulations.PloS one · 2019Article
- Developing Practical Therapeutic Strategies that Target Protein SUMOylation.Current drug targets · 2019Review
- Ubiquitin and Ubiquitin-like proteins in cardiac disease and protection.Current drug targets · 2018Review
- SIRT1 deacetylates the cardiac transcription factor Nkx2.5 and inhibits its transcriptional activity.Scientific reports · 2016Article
- Pias1 is essential for erythroid and vascular development in the mouse embryo.Developmental biology · 2016Article
- SUMOylation Regulates Growth Factor Independence 1 in Transcriptional Control and Hematopoiesis.Molecular and cellular biology · 2016Article
- Is Transthyretin a Regulator of Ubc9 SUMOylation?PloS one · 2016Article
- Fractal heterogeneity in minimal matrix models of scars modulates stiff-niche stem-cell responses via nuclear exit of a mechanorepressor.Nature materials · 2015Article
- Article
- NKX2-5 mutations in an inbred consanguineous population: genetic and phenotypic diversity.Scientific reports · 2015Article
Corrections and comments
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Authors and funding
11 authors at 6 institutions in 3 countries.
Funding
Abstract
Reversible post-translational protein modifications such as SUMOylation add complexity to cardiac transcriptional regulation. The homeodomain transcription factor Nkx2-5/Csx is essential for heart specification and morphogenesis. It has been previously suggested that SUMOylation of lysine 51 (K51) of Nkx2-5 is essential for its DNA binding and transcriptional activation. Here, we confirm that SUMOylation strongly enhances Nkx2-5 transcriptional activity and that residue K51 of Nkx2-5 is a SUMOylation target. However, in a range of cultured cell lines we find that a point mutation of K51 to arginine (K51R) does not affect Nkx2-5 activity or DNA binding, suggesting the existence of additional Nkx2-5 SUMOylated residues. Using biochemical assays, we demonstrate that Nkx2-5 is SUMOylated on at least one additional site, and this is the predominant site in cardiac cells. The second site is either non-canonical or a "shifting" site, as mutation of predicted consensus sites and indeed every individual lysine in the context of the K51R mutation failed to impair Nkx2-5 transcriptional synergism with SUMO, or its nuclear localization and DNA binding. We also observe SUMOylation of Nkx2-5 cofactors, which may be critical to Nkx2-5 regulation. Our data reveal highly complex regulatory mechanisms driven by SUMOylation to modulate Nkx2-5 activity.
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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.