The transcription factor E2F1 is the principal target of the tumor suppressor pRB. E2F1 promotes cell proliferation by activating growth-promoting genes upon growth stimulation. In contrast, E2F1 contributes to tumor suppression by activating tumor suppressor genes, such as , upon loss of pRB function, a major oncogenic change. The transactivation domain of E2F1 has previously been mapped to the C-terminal region. We show here that the N-terminal region of E2F1 is critical for the activation of tumor suppressor genes. Deletion of the N-terminal region dramatically compromised E2F1 activation of tumor suppressor genes. The N-terminal region showed transactivation ability when fused to the DNA-binding domain of GAL4. A search for novel interacting factors with the N-terminal region, using a yeast two-hybrid system, identified the general transcription factor GTF2H2. Overexpression of GTF2H2 enhanced E2F1 activation of tumor suppressor genes and induction of cell death. Conversely, the knockdown of GTF2H2 compromised both. E2F1 binding enhanced the binding of GTF2H2 to target promoters depending on the integrity of the N-terminal region. Taken together, these results suggest that the N-terminal region of E2F1 contains a novel transactivation domain that mediates the activation of tumor suppressor genes, at least in part, by recruiting GTF2H2.
Download full-text PDF |
Source |
---|---|
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11592155 | PMC |
http://dx.doi.org/10.3390/biom14111357 | DOI Listing |
J Biol Chem
December 2024
Department of Chemistry - Biochemistry, Johannes Gutenberg-University, 55128 Mainz, Germany; Institute of Molecular Physiology, Johannes Gutenberg-University, 55128 Mainz, Germany. Electronic address:
ABC transporters are membrane integral proteins that consist of a transmembrane (TMD) and nucleotide-binding domain (NBD). Two monomers (half-transporters) of the Bacillus subtilis ABC transporter BmrA (Bacillus multidrug-resistance ATP) dimerize to build a functional full-transporter. As all ABC exporters, BmrA uses the free energy of ATP hydrolysis to transport substrate molecules across the cell membrane.
View Article and Find Full Text PDFJ Biol Chem
December 2024
Cancer Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, California 92037, United States. Electronic address:
Missense mutations in the EPHA1 receptor tyrosine kinase have been identified in Alzheimer's patients. To gain insight into their potential role in disease pathogenesis, we investigated the effects of four of these mutations. We show that the P460L mutation in the second fibronectin type III (FN2) domain drastically reduces EPHA1 cell surface localization while increasing tyrosine phosphorylation of the cell surface localized receptor.
View Article and Find Full Text PDFJ Colloid Interface Sci
December 2024
Division of Computational Chemistry, Department of Chemistry, Lund University, P.O. Box 124, Lund, 22100, Sweden. Electronic address:
Unlabelled: This study investigates the interaction of KEIF, the intrinsically disordered N-terminal region of the magnesium transporter MgtA, with lipid bilayers mimicking cell membranes. Combining experimental techniques such as neutron reflectometry (NR), quartz-crystal microbalance with dissipation monitoring (QCM-D), synchrotron radiation circular dichroism (SRCD), and oriented circular dichroism (OCD), with molecular dynamics (MD) simulations, we characterized KEIF's adsorption behavior.
Hypothesis: KEIF undergoes conformational changes upon interacting with lipid bilayers, potentially influencing MgtA's function within the plasma membrane.
Front Endocrinol (Lausanne)
December 2024
Department of Cardiology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China.
Background: NT-proBNP (N-terminal pro-B-type natriuretic peptide), high-sensitivity cardiac troponin T (hs-troponin T), and high-sensitivity cardiac troponin I (hs-troponin I) have been widely recognized as significant cardiac biomarkers, and are increasingly being recommended for early risk identification in cardiovascular high-risk populations. The aim of our study was to evaluate the prevalence of elevated cardiac biomarkers (NT-proBNP, hs-troponin T, hs-troponin I) and their association with the risk of hyperuricemia in the general US adults without known cardiovascular disease. We further studied whether elevated cardiac biomarkers are associated with an increased risk of all-cause and cardiovascular mortality in individuals with or without hyperuricemia.
View Article and Find Full Text PDFCommun Biol
December 2024
College of Life Sciences, State Key Laboratory of Medicinal Chemical Biology, Frontiers Science Center for Cell Responses, Nankai University, Tianjin, China.
Encapsulin nanocompartments loaded with dedicated cargo proteins via unique targeting peptides, play a key role in stress resistance, iron storage and natural product biosynthesis. Mmp1 and cysteine desulfurase (Enc-CD) have been identified as the most abundant representatives of family 2 encapsulin systems. However, the molecular assembly, catalytic mechanism, and physiological functions of the Mmp1 encapsulin system have not been studied in detail.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!