ArticleProceedings of the National Academy of Sciences of the United States of America2006
Phosphorylation by PKA potentiates retinoic acid receptor alpha activity by means of increasing interaction with and phosphorylation by cyclin H/cdk7.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 74 citations in OpenAlex.
- Retinoic acid in health and disease.Signal transduction and targeted therapy · 2026Review
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- Retinoic acid signaling and metabolism in heart failure.American journal of physiology. Heart and circulatory physiology · 2025Review
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- Thyroid hormone receptor phosphorylation regulates acute fasting-induced suppression of the hypothalamic-pituitary-thyroid axis.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Review
- Insights into the activation mechanism of human estrogen-related receptor γ by environmental endocrine disruptors.Cellular and molecular life sciences : CMLS · 2019Article
- Differentiation therapy revisited.Nature reviews. Cancer · 2018Review
- Article
- RAR/RXR binding dynamics distinguish pluripotency from differentiation associated cis-regulatory elements.Nucleic acids research · 2015Article
- Synergy against PML-RARa: targeting transcription, proteolysis, differentiation, and self-renewal in acute promyelocytic leukemia.The Journal of experimental medicine · 2013Review
- Vitamin A and retinoid signaling: genomic and nongenomic effects.Journal of lipid research · 2013Review
- Phosphorylation of the retinoic acid receptor alpha induces a mechanical allosteric regulation and changes in internal dynamics.PLoS computational biology · 2013Article
- 8-CPT-cAMP/all-trans retinoic acid targets t(11;17) acute promyelocytic leukemia through enhanced cell differentiation and PLZF/RARα degradation.Proceedings of the National Academy of Sciences of the United States of America · 2013Article
- Article
- Regulation of the tumor suppressor PML by sequential post-translational modifications.Frontiers in oncology · 2012Article
- Retinoids regulate stem cell differentiation.Journal of cellular physiology · 2011Review
- A role for all-trans-retinoic acid in the early steps of lymphatic vasculature development.Journal of vascular research · 2011Article
- Molecular mechanisms of leukemia-associated protein degradation.Frontiers of medicine in China · 2010Review
- Acute promyelocytic leukaemia: novel insights into the mechanisms of cure.Nature reviews. Cancer · 2010Review
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Nuclear retinoic acid receptors (RARs) work as ligand-dependent heterodimeric RAR/retinoid X receptor transcription activators, which are targets for phosphorylations. The N-terminal activation function (AF)-1 domain of RARalpha is phosphorylated by the cyclin-dependent kinase (cdk) 7/cyclin H complex of the general transcription factor TFIIH and the C-terminal AF-2 domain by the cAMP-dependent protein kinase A (PKA). Here, we report the identification of a molecular pathway by which phosphorylation by PKA propagates cAMP signaling from the AF-2 domain to the AF-1 domain. The first step is the phosphorylation of S369, located in loop 9-10 of the AF-2 domain. This signal is transferred to the cyclin H binding domain (at the N terminus of helix 9 and loop 8-9), resulting in enhanced cyclin H interaction and, thereby, greater amounts of RARalpha phosphorylated at S77 located in the AF-1 domain by the cdk7/cyclin H complex. This molecular mechanism relies on the integrity of the ligand-binding domain and the cyclin H binding surface. Finally, it results in higher DNA-binding efficiency, providing an explanation for how cAMP synergizes with retinoic acid for transcription.
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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.