Evidence has revealed that transcription factors play essential roles in regulation of multiple cellular processes, including cell proliferation, metastasis, EMT, cancer stem cells and chemoresistance. Dysregulated expression levels of transcription factors contribute to tumorigenesis and malignant progression. The expression of transcription factors is tightly governed by several signaling pathways, noncoding RNAs and E3 ubiquitin ligases. Cancer stem cells (CSCs) have been validated in regulation of tumor metastasis, reoccurrence and chemoresistance in human cancer. Transcription factors have been verified to participate in regulation of CSC formation, including Oct4, SOX2, KLF4, c-Myc, Nanog, GATA, SALL4, Bmi-1, OLIG2, POU3F2 and FOX proteins. In this review article, we will describe the critical role of CSC-related transcription factors. We will further discuss which E3 ligases regulate the degradation of these CSC-related transcription factors and their underlying mechanisms. We also mentioned the functions and mechanisms of EMT-associated transcription factors such as ZEB1, ZEB2, Snail, Slug, Twist1 and Twist2. Furthermore, we highlight the therapeutic potential via targeting E3 ubiquitin ligases for modulation of these transcription factors.
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http://dx.doi.org/10.1016/j.semcancer.2022.11.002 | DOI Listing |
Elife
January 2025
Department of Molecular and Cell Biology, Berkeley, United States.
Type II nuclear receptors (T2NRs) require heterodimerization with a common partner, the retinoid X receptor (RXR), to bind cognate DNA recognition sites in chromatin. Based on previous biochemical and overexpression studies, binding of T2NRs to chromatin is proposed to be regulated by competition for a limiting pool of the core RXR subunit. However, this mechanism has not yet been tested for endogenous proteins in live cells.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
January 2025
Department of Chemical Engineering, Stanford University, Stanford, CA 94305.
DNA methylation is a crucial epigenetic modification that orchestrates chromatin remodelers that suppress transcription, and aberrations in DNA methylation result in a variety of conditions such as cancers and developmental disorders. While it is understood that methylation occurs at CpG-rich DNA regions, it is less understood how distinct methylation profiles are established within various cell types. In this work, we develop a molecular-transport model that depicts the genomic exploration of DNA methyltransferase within a multiscale DNA environment, incorporating biologically relevant factors like methylation rate and CpG density to predict how patterns are established.
View Article and Find Full Text PDFMol Neurobiol
January 2025
Hebei Medical University-Galway University Stem Cell Research Center, Hebei Medical University, Shijiazhuang, 050017, Hebei Province, China.
This study utilises amyotrophic lateral sclerosis (ALS) and Parkinson's disease (PD) human brain samples from the GEO database and employs differential expression gene (DEG) analysis to identify genes that are pivotal in both neurodegenerative diseases. Through in depth GO and KEGG enrichment analyses, we elucidated the biological functions and potential pathways associated with these DEGs. Furthermore, by constructing protein‒protein interaction networks, we highlight the significance of shared DEGs in both cellular physiology and disease contexts.
View Article and Find Full Text PDFElife
January 2025
Department of Pediatrics, the Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China.
Type 1 diabetes mellitus (T1DM), known as insulin-dependent diabetes mellitus, is characterized by persistent hyperglycemia resulting from damage to the pancreatic β cells and an absolute deficiency of insulin, leading to multi-organ involvement and a poor prognosis. The progression of T1DM is significantly influenced by oxidative stress and apoptosis. The natural compound eugenol (EUG) possesses anti-inflammatory, anti-oxidant, and anti-apoptotic properties.
View Article and Find Full Text PDFCells
January 2025
Research Institute of Medical and Health Sciences, University of Sharjah, Sharjah P.O. Box 27272, United Arab Emirates.
The Kynurenine pathway is crucial in metabolizing dietary tryptophan into bioactive compounds known as kynurenines, which have been linked to glucose homeostasis. The aryl hydrocarbon receptor (AhR) has recently emerged as the endogenous receptor for the kynurenine metabolite, kynurenic acid (KYNA). However, the specific role of AhR in pancreatic β-cells remains largely unexplored.
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