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Parental genomic imprinting causes preferential expression of one of the two parental alleles. In mammals, differential sex-dependent deposition of silencing DNA methylation marks during gametogenesis initiates a new cycle of imprinting. Parental genomic imprinting has been detected in plants and relies on DNA methylation by the methyltransferase MET1. However, in contrast to mammals, plant imprints are created by differential removal of silencing marks during gametogenesis. In Arabidopsis, DNA demethylation is mediated by the DNA glycosylase DEMETER (DME) causing activation of imprinted genes at the end of female gametogenesis. On the basis of genetic interactions, we show that in addition to DME, the plant homologs of the human Retinoblastoma (Rb) and its binding partner RbAp48 are required for the activation of the imprinted genes FIS2 and FWA. This Rb-dependent activation is mediated by direct transcriptional repression of MET1 during female gametogenesis. We have thus identified a new mechanism required for imprinting establishment, outlining a new role for the Retinoblastoma pathway, which may be conserved in mammals.
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http://dx.doi.org/10.1371/journal.pbio.0060194 | DOI Listing |
Genes (Basel)
August 2025
Department of Biomedical Sciences, School of Biological and Environmental Sciences, Kwansei Gakuin University, 1 Gakuen Uegahara, Sanda 669-1330, Japan.
Background: DEAD/H box 5 (DDX5) serves as a transcriptional coactivator for several transcription factors including E2F1, the primary target of the tumor suppressor pRB. E2F1 physiologically activated by growth stimulation activates growth-related genes and promotes cell proliferation. In contrast, upon loss of pRB function due to oncogenic changes, E2F1 is activated out of restraint by pRB (deregulated E2F1) and stimulates tumor suppressor genes such as , which activates the tumor suppressor p53, to suppress tumorigenesis.
View Article and Find Full Text PDFBiomolecules
August 2025
School of Exercise and Health, Shanghai University of Sport, Shanghai 200438, China.
PR/SET domain 2 (PRDM2)/RIZ is a member of the histone/protein methyltransferases (PRDMs) superfamily. Discovered to have the ability to bind retinoblastoma in the mid-1990s, PRDM2 was assumed to play a role in neuronal development. Like other family members characterized by a conserved N-terminal PR structural domain and a classical C2H2 zinc-finger array at the C-terminus, PRDM2 encodes two major protein types, the RIZ1 and RIZ2 isoforms.
View Article and Find Full Text PDFStructure
August 2025
Department of Chemistry, University of Pavia, Via Taramelli 12, 27100 Pavia, Italy. Electronic address:
Essential chaperones heat shock protein 70 (Hsp70) and heat shock protein 90 (Hsp90) collaborate in oncoprotein folding. Dual inhibition of these chaperones has shown synergy in preclinical studies but remains challenging to achieve. Using a computational approach, we designed peptides mimicking the predicted unfolding regions of Kinase CDK4, a client protein of both Hsp70 and Hsp90.
View Article and Find Full Text PDFAsian Pac J Cancer Prev
August 2025
Department of Oral Biology, Faculty of Dentistry, Mahidol University, Bangkok, Yothi Road, Rajthewi District, Bangkok 10400, Thailand.
Objective: Ameloblastoma (AM) is a well-known benign odontogenic tumor recognized for its aggressive nature, believed to originate from tooth-forming tissue or the dental follicle (DF). Phosphoproteins are crucial for cellular signaling, enabling intracellular communication and regulating various physiological processes. In cancer, phosphoproteins are fundamental to both pathogenesis and pathophysiology.
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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