The homeodomain protein TGIF has been implicated in the negative regulation of TGF-beta signaling. In this study, we report an unexpected role of TGIF in the inhibition of Smad2 phosphorylation, which occurs by a mechanism independent of its association with Smad2. This inhibitory function of TGIF is executed in concert with c-Jun, which facilitates the interaction of TGIF with cPML, resulting in the nuclear sequestration of cPML and the disruption of the cPML-SARA complex. Notably, knockdown of TGIF by siRNA caused increased association of cPML with SARA and cytoplasmic accumulation of cPML. Furthermore, c-Jun(-/-) fibroblasts exhibit enhanced association of cPML with SARA. c-Jun(-/-) fibroblasts also lose their sensitivity to TGIF-mediated disruption of the cPML-SARA complex and of nuclear sequestration of cPML. We suggest that the interaction of TGIF with cPML through c-Jun may negatively regulate TGF-beta signaling through controlling the localization of cPML and, consequently, the assembly of the cPML-SARA complex.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.molcel.2006.06.018 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
ERBB4 selectively amplifies TGF-β pro-metastatic responses.
Cell Rep
January 2025
MOE Key Laboratory of Biosystems Homeostasis & Protection, and Zhejiang Provincial Key Laboratory of Cancer Molecular Cell Biology, Life Sciences Institute, Zhejiang University, Hangzhou, Zhejiang 310058, China; Center for Life Sciences, Shaoxing Institute, Zhejiang University, Shaoxing, Zhejiang 321000, China; Cancer Center, Zhejiang University, Hangzhou, Zhejiang 310058, China; The Second Affiliated Hospital, Zhejiang University, Hangzhou, Zhejiang 310009, China. Electronic address:
Transforming growth factor β (TGF-β) is well known to play paradoxical roles in tumorigenesis as it has both growth-inhibitory and pro-metastatic effects. However, the underlying mechanisms of how TGF-β drives the opposing responses remain largely unknown. Here, we report that ERBB4, a member of the ERBB receptor tyrosine kinase family, specifically promotes TGF-β's metastatic response but not its anti-growth response.
View Article and Find Full Text PDFScreening of Anti-Hair Loss Plant Raw Materials Based on Reverse Network Pharmacology and Experimental Validation.
Curr Issues Mol Biol
January 2025
Beijing Key Laboratory of Plant Resources Research and Development, School of Light Industry Science and Engineering, Beijing Technology and Business University, Beijing 100048, China.
Hair loss is one of the skin conditions that can affect people's mental health. Plant raw material extracts are of great interest due to their safety. In this study, we utilize reverse network pharmacology to screen for key targets of the Wnt/β-catenin signaling pathway and the TGFβ/BMP signaling pathway, as well as key differential lipids, for plant raw materials selection.
View Article and Find Full Text PDFGene-Environment Interaction: Small Deletions (DELs) and Transcriptomic Profiles in Non-Melanoma Skin Cancer (NMSC) and Potential Implications for Therapy.
Cells
January 2025
Institute for Population and Precision Health (IPPH), University of Chicago, Chicago, IL 60637, USA.
Arsenic (As) is a risk factor for non-melanoma skin cancer (NMSC). From a six-year follow-up study on 7000 adults exposed to As, we reported the associations of single-nucleotide variation in tumor tissue and gene expression. Here, we identify the associations of small deletions (DELs) and transcriptomic profiles in NMSC.
View Article and Find Full Text PDFmiR-1233-3p Inhibits Angiopoietin-1-Induced Endothelial Cell Survival, Migration, and Differentiation.
Cells
January 2025
Meakins-Christie Laboratories, Department of Medicine, McGill University, Montreal, QC H4A 3J1, Canada.
Angiopoietin-1 (Ang-1) and its receptor Tie-2 promote vascular integrity and angiogenesis. MicroRNAs (miRNAs) are involved in the regulation of many cellular functions, including endothelial cell (EC) survival, proliferation, and differentiation. Several reports indicate that these effects of miRNAs on EC functions are mediated through the modulation of angiogenesis factor signaling including that of vascular endothelial growth factor (VEGF).
View Article and Find Full Text PDFGlycogen homeostasis and mitochondrial DNA expression require motor neuron to muscle TGF-β/Activin signaling in Drosophila.
iScience
January 2025
Department of Genetics, Cell Biology and Development, University of Minnesota, Minneapolis, MN 55455, USA.
Maintaining metabolic homeostasis requires coordinated nutrient utilization between intracellular organelles and across multiple organ systems. Many organs rely heavily on mitochondria to generate (ATP) from glucose, or stored glycogen. Proteins required for ATP generation are encoded in both nuclear and mitochondrial DNA (mtDNA).
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!