ArticleMolecular endocrinology (Baltimore, Md.)2007
Response of SMRT (silencing mediator of retinoic acid and thyroid hormone receptor) and N-CoR (nuclear receptor corepressor) corepressors to mitogen-activated protein kinase kinase kinase cascades is determined by alternative mRNA splicing.
Article in Molecular endocrinology (Baltimore, Md.), 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 39 citations in OpenAlex.
- miR-1 as a Key Epigenetic Regulator in Early Differentiation of Cardiac Sinoatrial Region.International journal of molecular sciences · 2024Article
- Review
- The pan-cancer lncRNA PLANE regulates an alternative splicing program to promote cancer pathogenesis.Nature communications · 2021Article
- Specific ablation of the NCoR corepressor δ splice variant reveals alternative RNA splicing as a key regulator of hepatic metabolism.PloS one · 2020Article
- Evolution of NCoR-1 and NCoR-2 corepressor alternative mRNA splicing in placental mammals.BMC research notes · 2019Article
- Regulation of corepressor alternative mRNA splicing by hormonal and metabolic signaling.Molecular and cellular endocrinology · 2015Article
- The ability of thyroid hormone receptors to sense t4 as an agonist depends on receptor isoform and on cellular cofactors.Molecular endocrinology (Baltimore, Md.) · 2014Article
- Thyroid hormone signaling in vivo requires a balance between coactivators and corepressors.Molecular and cellular biology · 2014Article
- Vitamin A and retinoid signaling: genomic and nongenomic effects.Journal of lipid research · 2013Review
- Emerging roles of the corepressors NCoR1 and SMRT in homeostasis.Genes & development · 2013Review
- Elevated nuclear expression of the SMRT corepressor in breast cancer is associated with earlier tumor recurrence.Breast cancer research and treatment · 2012Article
- SMRTε, a corepressor variant, interacts with a restricted subset of nuclear receptors, including the retinoic acid receptors α and β.Molecular and cellular endocrinology · 2012Article
- Alternative mRNA splicing of corepressors generates variants that play opposing roles in adipocyte differentiation.The Journal of biological chemistry · 2011Article
- Aberrant corepressor interactions implicated in PML-RAR(alpha) and PLZF-RAR(alpha) leukemogenesis reflect an altered recruitment and release of specific NCoR and SMRT splice variants.The Journal of biological chemistry · 2011Article
- Regulation of SMRT corepressor dimerization and composition by MAP kinase phosphorylation.Molecular and cellular endocrinology · 2011Article
- Article
- Crosstalk in inflammation: the interplay of glucocorticoid receptor-based mechanisms and kinases and phosphatases.Endocrine reviews · 2009Review
- The thyroid hormone receptor recruits NCoR via widely spaced receptor-interacting domains.Molecular and cellular endocrinology · 2009Article
- Thyroid hormone receptor mutations found in renal clear cell carcinomas alter corepressor release and reveal helix 12 as key determinant of corepressor specificity.Molecular endocrinology (Baltimore, Md.) · 2009Article
- The nuclear corepressor, NCoR, regulates thyroid hormone action in vivo.Proceedings of the National Academy of Sciences of the United States of America · 2008Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
The SMRT (silencing mediator of retinoic acid and thyroid hormone receptor) and N-CoR (nuclear receptor corepressor) corepressors are important mediators of transcriptional repression by nuclear hormone receptors. SMRT is regulated by MAPK kinase kinase (MAPKKK) cascades that induce its release from its receptor partners, its export from nucleus to cytoplasm, and derepression of target gene expression. Intriguingly, the otherwise closely related N-CoR is refractory to MAPKKK signaling under the same conditions. However, both SMRT and N-CoR are expressed as a series of alternatively spliced protein variants differing in structure and function. We have now characterized the impact of this alternative mRNA splicing on the corepressor response to MAPKKK signaling. Whereas the SMRTalpha, SMRTtau, and SMRTsp2 splice variants are released from their nuclear receptor partners in response to MAPKKK activation, the SMRTsp18 variant, which resembles N-CoR in its overall molecular architecture, is relatively refractory to this kinase-induced release. Alternative splicing of N-CoR, in contrast, had only minimal effects on the resistance of this corepressor to MAPKKK inhibition. Notably, all of the SMRT splice variants examined redistributed from nucleus to cytoplasm in response to MAPKKK cascade signaling, but none of the N-CoR splice variants did so. Different tiers of the MAPKKK cascade hierarchy contributed to these different aspects of corepressor regulation, with MAP/ERK kinase kinase 1 and MAP/ERK kinase 1 regulating subcellular redistribution and ERK2 regulating nuclear receptor-corepressor interaction. We conclude that cells can customize their transcriptional response to MAPKKK cascade signaling by selective expression of the SMRT or N-CoR locus, by selective utilization of a specific corepressor splice variant, and by selective exploitation of specific tiers of the MAPK cascade.
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