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CK2-mediated DEK Phosphorylation Drives PBX3 Overexpression: A Core Event in Hematopoietic Stem Cell-to-Leukemia Stem Cell Transformation

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE309285 | GEO | 2025/09/30

REPOSITORIES: GEO

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CK2-mediated DEK Phosphorylation Drives PBX3 Overexpression: A Core Event in Hematopoietic Stem Cell-to-Leukemia Stem Cell Transformation [ATAC-seq]

Project description:Leukemia stem cells (LSCs) possess self-renewal capacity and are largely refractory to conventional chemotherapy, thereby driving relapse and treatment failure in acute myeloid leukemia (AML). Here, we identify DEK as a crucial oncogenic factor aberrantly overexpressed in relapsed AML, with markedly increased phosphorylation by casein kinase 2 (CK2), correlating with poor patient prognosis. Using human AML cells and mouse models, we demonstrate that loss of DEK or phospho-mutants DEK, specifically at Ser306/Ser308/Ser311/Ser312 induces AML cells proliferation, differentiation, and weakened LSCs stemness. Mechanistically, phosphorylated DEK recruits GABPA to activate PBX3 transcription, thereby driving a leukemic transcriptional program. Importantly, targeting DEK or pharmacologic inhibition of CK2 using the specific inhibitor CX-4945 disrupts DEK phosphorylation and markedly sensitizes AML cells to venetoclax treatment, providing a rationale for a potential combination therapeutic strategy. Collectively, our findings uncover a unique and critical role of phosphorylated DEK as a transcriptional coactivator in AML and highlight the CK2-DEK/GABPA-PBX3 axis as a promising therapeutic target for AML.

2025-09-30 | GSE309177 | GEO

CK2-mediated DEK Phosphorylation Drives PBX3 Overexpression: A Core Event in Hematopoietic Stem Cell-to-Leukemia Stem Cell Transformation [RNA-seq]

2025-09-30 | GSE309176 | GEO

CK2-mediated DEK Phosphorylation Drives PBX3 Overexpression: A Core Event in Hematopoietic Stem Cell-to-Leukemia Stem Cell Transformation [CUT&Tag]

2025-09-30 | GSE309284 | GEO

CK2-mediated DEK Phosphorylation Drives PBX3 Overexpression: A Core Event in Hematopoietic Stem Cell-to-Leukemia Stem Cell Transformation

Project description:CK2-mediated DEK Phosphorylation Drives PBX3 Overexpression: A Core Event in Hematopoietic Stem Cell-to-Leukemia Stem Cell Transformation

| PRJNA1335085 | ENA

CK2-mediated DEK Phosphorylation Drives PBX3 Overexpression: A Core Event in Hematopoietic Stem Cell-to-Leukemia Stem Cell Transformation [CUT&Tag]

Project description:CK2-mediated DEK Phosphorylation Drives PBX3 Overexpression: A Core Event in Hematopoietic Stem Cell-to-Leukemia Stem Cell Transformation [CUT&Tag]

| PRJNA1335095 | ENA

CK2-mediated DEK Phosphorylation Drives PBX3 Overexpression: A Core Event in Hematopoietic Stem Cell-to-Leukemia Stem Cell Transformation [RNA-seq]

Project description:CK2-mediated DEK Phosphorylation Drives PBX3 Overexpression: A Core Event in Hematopoietic Stem Cell-to-Leukemia Stem Cell Transformation [RNA-seq]

| PRJNA1334263 | ENA

CK2-mediated DEK Phosphorylation Drives PBX3 Overexpression: A Core Event in Hematopoietic Stem Cell-to-Leukemia Stem Cell Transformation [ATAC-seq]

Project description:CK2-mediated DEK Phosphorylation Drives PBX3 Overexpression: A Core Event in Hematopoietic Stem Cell-to-Leukemia Stem Cell Transformation [ATAC-seq]

| PRJNA1334266 | ENA

Overexpression of the cellular DEK protein promotes epithelial transformation in vitro and in vivo.

Project description:High levels of expression of the human DEK gene have been correlated with numerous human malignancies. Intracellular DEK functions have been described in vitro and include DNA supercoiling, DNA replication, RNA splicing, and transcription. We have shown that DEK also suppresses cellular senescence, apoptosis, and differentiation, thus promoting cell growth and survival in monolayer and organotypic epithelial raft models. Such functions are likely to contribute to cancer, but direct evidence to implicate DEK as an oncogene has remained elusive. Here, we show that in line with an early role in tumorigenesis, murine papilloma formation in a classical chemical carcinogenesis model was reduced in DEK knockout mice. Additionally, human papillomavirus E6/E7, hRas, and DEK cooperated in the transformation of keratinocytes in soft agar and xenograft establishment, thus also implicating DEK in tumor promotion at later stages. Finally, adenoviral DEK depletion via short hairpin RNA expression resulted in cell death in human tumor cells in vitro and in vivo, but did not significantly affect differentiated epithelial cells. Taken together, our data uncover oncogenic DEK activities as postulated from its frequent up-regulation in human malignancies, and suggest that the targeted suppression of DEK may become a strategic approach to the treatment of cancer.

| S-EPMC2650744 | biostudies-literature

CRY Drives Cyclic CK2-Mediated BMAL1 Phosphorylation to Control the Mammalian Circadian Clock.

Project description:Intracellular circadian clocks, composed of clock genes that act in transcription-translation feedback loops, drive global rhythmic expression of the mammalian transcriptome and allow an organism to anticipate to the momentum of the day. Using a novel clock-perturbing peptide, we established a pivotal role for casein kinase (CK)-2-mediated circadian BMAL1-Ser90 phosphorylation (BMAL1-P) in regulating central and peripheral core clocks. Subsequent analysis of the underlying mechanism showed a novel role of CRY as a repressor for protein kinase. Co-immunoprecipitation experiments and real-time monitoring of protein-protein interactions revealed that CRY-mediated periodic binding of CK2β to BMAL1 inhibits BMAL1-Ser90 phosphorylation by CK2α. The FAD binding domain of CRY1, two C-terminal BMAL1 domains, and particularly BMAL1-Lys537 acetylation/deacetylation by CLOCK/SIRT1, were shown to be critical for CRY-mediated BMAL1-CK2β binding. Reciprocally, BMAL1-Ser90 phosphorylation is prerequisite for BMAL1-Lys537 acetylation. We propose a dual negative-feedback model in which a CRY-dependent CK2-driven posttranslational BMAL1-P-BMAL1 loop is an integral part of the core clock oscillator.

| S-EPMC4642984 | biostudies-literature

Overexpression of the human DEK oncogene reprograms cellular metabolism and promotes glycolysis.

Project description:The DEK oncogene is overexpressed in many human malignancies including at early tumor stages. Our reported in vitro and in vivo models of squamous cell carcinoma have demonstrated that DEK contributes functionally to cellular and tumor survival and to proliferation. However, the underlying molecular mechanisms remain poorly understood. Based on recent RNA sequencing experiments, DEK expression was necessary for the transcription of several metabolic enzymes involved in anabolic pathways. This identified a possible mechanism whereby DEK may drive cellular metabolism to enable cell proliferation. Functional metabolic Seahorse analysis demonstrated increased baseline and maximum extracellular acidification rates, a readout of glycolysis, in DEK-overexpressing keratinocytes and squamous cell carcinoma cells. DEK overexpression also increased the maximum rate of oxygen consumption and therefore increased the potential for oxidative phosphorylation (OxPhos). To detect small metabolites that participate in glycolysis and the tricarboxylic acid cycle (TCA) that supplies substrate for OxPhos, we carried out NMR-based metabolomics studies. We found that high levels of DEK significantly reprogrammed cellular metabolism and altered the abundances of amino acids, TCA cycle intermediates and the glycolytic end products lactate, alanine and NAD+. Taken together, these data support a scenario whereby overexpression of the human DEK oncogene reprograms keratinocyte metabolism to fulfill energy and macromolecule demands required to enable and sustain cancer cell growth.

| S-EPMC5448751 | biostudies-literature

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