A large body of work has shown that MYB acts as a master transcription regulator in hematopoietic cells and has pinpointed MYB as a potential drug target for acute myeloid leukemia (AML). Here, we have examined the MYB-inhibitory potential of the HDAC inhibitor LAQ824, which was identified in a screen for novel MYB inhibitors. We show that nanomolar concentrations of LAQ824 and the related HDAC inhibitors vorinostat and panobinostat interfere with MYB function in two ways, by inducing its degradation and inhibiting its activity. Reporter assays show that the inhibition of MYB activity by LAQ824 involves the MYB transactivation domain and the cooperation of MYB with co-activator p300, a key MYB interaction partner and driver of MYB activity. In AML cells, LAQ824-induced degradation of MYB is accompanied by expression of myeloid differentiation markers and apoptotic and necrotic cell death. The ability of LAQ824 to inhibit MYB activity is supported by the observation that down-regulation of direct MYB target genes and occurs without apparent decrease of MYB expression already after 2 h of treatment with LAQ824. Furthermore, ectopic expression of an activated version of MYB In HL60 cells counteracts the induction of myeloid differentiation by LAQ824. Overall, our data identify LAQ824 and related HDAC inhibitors as potent MYB-inhibitory agents that exert dual effects on MYB expression and activity in AML cells.
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http://dx.doi.org/10.1016/j.bbadva.2021.100034 | DOI Listing |
BMC Plant Biol
January 2025
Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing, 100193, China.
Background: Root rot is a major disease affecting alfalfa (Medicago sativa L.), causing significant yield losses and economic damage. The primary pathogens include Fusarium spp.
View Article and Find Full Text PDFBMC Plant Biol
January 2025
College of Civil and Transportation Engineering, Shenzhen University, Shenzhen, 518060, China.
Background: Zinc finger homeodomain (ZF-HD) belongs to the plant-specific transcription factor (TF) family and is widely involved in plant growth, development and stress responses. Despite their importance, a comprehensive identification and analysis of ZF-HD genes in the soybean (Glycine max) genome and their possible roles under abiotic stress remain unexplored.
Results: In this study, 51 ZF-HD genes were identified in the soybean genome that were unevenly distributed on 17 chromosomes.
Nat Chem Biol
January 2025
Department of Gynecology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
The regressed arms of reversed replication forks exhibit structural similarities to one-ended double-stranded breaks and need to be protected against uncontrolled nucleolytic degradation. Here, we identify MSANTD4 (Myb/SANT-like DNA-binding domain-containing protein 4), a functionally uncharacterized protein that uniquely counters the replication protein A (RPA)-Bloom (BLM)/Werner syndrome helicase (WRN)-DNA replication helicase/nuclease 2 (DNA2) complex to safeguard reversed replication forks from detrimental degradation, independently of the breast cancer susceptibility proteins (BRCA1/2)-DNA repair protein RAD51 pathway. MSANTD4 specifically interacts with the junctions between single-stranded DNA (ssDNA) and double-stranded DNA (dsDNA) in DNA substrates harboring a 3' overhang, which resemble the structural features of regressed arms processed by WRN-DNA2.
View Article and Find Full Text PDFBMC Genom Data
January 2025
Institute of Biotechnology and Food Science, Hebei Academy of Agriculture and Forestry Sciences/Hebei Key Laboratory of Plant Genetic Engineering, Shijiazhuang, 050000, China.
Background: Wheat seeds display different colors due to the types and contents of anthocyanins, which is closely related to anthocyanin metabolism. In this study, a transcriptomic and metabolomic analysis between white and purple color wheat pericarp aimed to explore some key genes and metabolites involved in anthocyanin metabolism.
Results: Two wheat cultivars, a white seed cultivar Shiluan02-1 and purple seed cultivar Hengzi151 were used to identify the variations in differentially expressed genes (DEGs) and differentially accumulated flavonoids (DAFs).
J Liq Biopsy
December 2024
Dr. Nasser Ibrahim Al-Rashid Orbital Vision Research Center, Bascom Palmer Eye Institute, Miller School of Medicine, University of Miami, Miami, FL 33136, USA.
Adenoid cystic carcinoma (ACC) is a rare and lethal malignancy that originates in secretory glands of the head and neck. A prominent molecular feature of ACC is the overexpression of the proto-oncogene MYB. ACC has a poor long-term survival due to its high propensity for recurrence and protracted metastasis.
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