The core promoters of protein-encoding genes play a central role in regulating transcription. M1BP is a transcriptional activator that associates with a core promoter element known as Motif 1 that resides at thousands of genes in To gain insight into how M1BP functions, we identified an interacting protein called GFZF. GFZF had been previously identified in genetic screens for factors involved in maintenance of hybrid inviability, the G-M DNA damage checkpoint, and RAS/mitogen-activated protein kinase (MAPK) signaling, but its contribution to these processes was unknown. Here, we show that GFZF resides in the nucleus and functions as a transcriptional coactivator. In addition, we show that GFZF is a glutathione -transferase (GST). Thus, GFZF is the first transcriptional coactivator with intrinsic GST activity, and its identification as a transcriptional coactivator provides an explanation for its role in numerous biological processes.
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http://dx.doi.org/10.1128/MCB.00476-17 | DOI Listing |
Int J Mol Sci
January 2025
Institute of Pathology, Medical Faculty Heidelberg, Heidelberg University, 69120 Heidelberg, Germany.
The oncogenes yes-associated protein () and transcriptional coactivator with PDZ-binding motif () are potent liver oncogenes. Because gene mutations cannot fully explain their nuclear enrichment, we aim to understand which mechanisms cause activation in liver cancer cells. The combination of proteomics and functional screening identified numerous apical cell polarity complex proteins interacting with YAP and TAZ.
View Article and Find Full Text PDFSci Rep
January 2025
Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA, 02129, USA.
Genotype-informed anticancer therapies such as BRAF inhibitors can show remarkable clinical efficacy in BRAF-mutant melanoma; however, drug resistance poses a major hurdle to successful cancer treatment. Many resistance events to targeted therapies have been identified, suggesting a complex path to improve therapeutics. Here, we showed the utility of a piggyBac transposon activation mutagenesis screen for the efficient identification of genes that are resistant to BRAF inhibition in melanoma.
View Article and Find Full Text PDFMol Biol Rep
January 2025
Cancer Research Laboratory, Department of Zoology, University of Calcutta, 35 Ballygunge Circular Road, Kolkata, West Bengal, 700019, India.
Background: Current treatment strategies for hormone-dependent breast cancers, including adjuvant endocrine therapy, often fail due to persistence of breast cancer stem cells (brCSCs), which are significant contributors to tumor recurrence and treatment resistance. Therefore, gaining deeper insights into the molecular regulators driving breast cancer aggressiveness is important. Moreover, given the complexities and expenses involved in developing new pharmacological agents, the strategic repurposing of existing FDA-approved drugs to target these key molecular pathways presents a compelling approach for identifying novel therapeutic interventions aimed at mitigating tumor refractoriness.
View Article and Find Full Text PDFCells
January 2025
Department of Biochemistry, Dongguk University College of Medicine, 123 Dongdae-ro, Gyeongju 38066, Republic of Korea.
An actin-binding protein, known as Calponin 3 (CNN3), modulates the remodeling of the actin cytoskeleton, a fundamental process for the maintenance of skeletal muscle homeostasis. Although the roles of CNN3 in actin remodeling have been established, its biological significance in myoblast differentiation remains largely unknown. This study investigated the functional significance of CNN3 in myogenic differentiation, along with its effects on actin remodeling and mechanosensitive signaling in C2C12 myoblasts.
View Article and Find Full Text PDFFront Immunol
January 2025
Immunology Research Center, National Health Research Institute, Zhunan, Taiwan.
CASK, a MAGUK family scaffold protein, regulates gene expression as a transcription co-activator in neurons. However, the mechanism of CASK nucleus translocation and the regulatory function of CASK in myeloid cells remains unclear. Here, we investigated its role in H5N1-infected macrophages.
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