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Proteins perform their activities in cells by the cooperation within protein complexes. For this reason, it is important to investigate protein-protein interactions to receive insights in physiological processes. A multitude of proteins are involved in the regulation of the cell cycle. Specific key factors participating here are members of the E2F transcription factors. Using an in vivo protein-protein complex detection assay, which comprises mass spectrometric and immunological techniques, we detected a number of known as well as new protein-protein interactions. We describe here for the first time protein complexes containing the corepressor Alien and members of the E2F transcription factor family. Furthermore, we assessed the functional relevance and show a repression of the transcriptional activity of E2F by Alien. Additionally, we detected new interactions that link endogenously expressed Alien with the tumor suppressor retinoblastoma protein (pRB) and with proteins involved in cell cycle regulation.
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http://dx.doi.org/10.1021/pr060500c | DOI Listing |
Front Plant Sci
August 2025
College of Life Sciences, Leshan Normal University, Leshan, Sichuan, China.
(Eukaryotic Transcription Factor 2/Dimerization Partner) refers to a class of protein complexes that play a pivotal role in the regulation of gene transcription in eukaryotes. In higher plants, transcription factors are of vital significance in mediating responses to environmental stresses. Based on differences in their conserved structural domains, they can be categorized into three subgroups: E2F, DP, and DEL (DP-E2F-like).
View Article and Find Full Text PDFCell Death Dis
August 2025
Department of Molecular Oncology, Graduate School of Medicine, Chiba University, Chiba-shi, Japan.
SETD1A is a member of the KMT2 histone H3K4 methyltransferase family of mammalian proteins. Aberrant SETD1A expression is associated with a poor prognosis in patients with gastric cancer (GC). We found that the catalytic domain of SETD1A is nonessential for GC cell proliferation, whereas the non-catalytic FLOS domain is essential.
View Article and Find Full Text PDFCell Death Differ
August 2025
Molecular Oncology, Faculty of Medicine, University of Leipzig, Leipzig, Germany.
BRCA1 and BRCA2 proteins are crucial for DNA repair through homologous recombination (HR), which predominantly takes place during S and G phases. Their expression is tightly regulated to ensure HR occurs exclusively within these phases. While these proteins are well-established tumor suppressors in hereditary breast and ovarian cancers, their inactivation is rare across all sporadic cancers.
View Article and Find Full Text PDFGenes Dis
November 2025
Department of Orthopedics, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150081, China.
Understanding metastatic osteosarcoma relies on defining the complexity of cell types, their associated molecular profiles, and interactions among cells in the tumor microenvironment. Here, we integrated single-cell and bulk gene expression datasets and revealed that metastatic lesions were highly enriched for osteoblasts (OB). Under the regulation of E2F family members, OB cells harbored enhanced proliferation activity and high differentiation potential.
View Article and Find Full Text PDFJ Med Chem
August 2025
Circle Pharma, Inc., 169 Harbor Way, South San Francisco, California 94080, United States.
The cyclin-dependent kinase (CDK)/retinoblastoma protein (RB)/early region 2 binding factor (E2F) axis forms the core transcriptional machinery driving cell cycle progression. Alterations in or other pathway members occur in many cancers, resulting in heightened oncogenic E2F activity. The activity of E2F is regulated by RxL-mediated binding to the hydrophobic patch (HP) of Cyclin A; blocking this interaction results in the hyperactivation of E2F and synthetic lethality in E2F-driven tumors.
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