Unlike Its Paralog LEDGF/p75, HRP-2 Is Dispensable for MLL-R Leukemogenesis but Important for Leukemic Cell Survival.

Abstract:

:HDGF-related protein 2 (HRP-2) is a member of the Hepatoma-Derived Growth Factor-related protein family that harbors the structured PWWP and Integrase Binding Domain, known to associate with methylated histone tails or cellular and viral proteins, respectively. Interestingly, HRP-2 is a paralog of Lens Epithelium Derived Growth Factor p75 (LEDGF/p75), which is essential for MLL-rearranged (MLL-r) leukemia but dispensable for hematopoiesis. Sequel to these findings, we investigated the role of HRP-2 in hematopoiesis and MLL-r leukemia. Protein interactions were investigated by co-immunoprecipitation and validated using recombinant proteins in NMR. A systemic knockout mouse model was used to study normal hematopoiesis and MLL-ENL transformation upon the different HRP-2 genotypes. The role of HRP-2 in MLL-r and other leukemic, human cell lines was evaluated by lentiviral-mediated miRNA targeting HRP-2. We demonstrate that MLL and HRP-2 interact through a conserved interface, although this interaction proved less dependent on menin than the MLL-LEDGF/p75 interaction. The systemic HRP-2 knockout mice only revealed an increase in neutrophils in the peripheral blood, whereas the depletion of HRP-2 in leukemic cell lines and transformed primary murine cells resulted in reduced colony formation independently of MLL-rearrangements. In contrast, primary murine HRP-2 knockout cells were efficiently transformed by the MLL-ENL fusion, indicating that HRP-2, unlike LEDGF/p75, is dispensable for the transformation of MLL-ENL leukemogenesis but important for leukemic cell survival.

journal_name

Cells

journal_title

Cells

authors

Van Belle S,El Ashkar S,Čermáková K,Matthijssens F,Goossens S,Canella A,Hodges CH,Christ F,De Rijck J,Van Vlierberghe P,Veverka V,Debyser Z

doi

10.3390/cells10010192

subject

Has Abstract

pub_date

2021-01-19 00:00:00

issue

1

issn

2073-4409

pii

cells10010192

journal_volume

10

pub_type

杂志文章

相关文献

Cells文献大全
  • Membrane Transporters for Amino Acids as Players of Cancer Metabolic Rewiring.

    abstract::Cancer cells perform a metabolic rewiring to sustain an increased growth rate and compensate for the redox stress caused by augmented energy metabolism. The metabolic changes are not the same in all cancers. Some features, however, are considered hallmarks of this disease. As an example, all cancer cells rewire the am...

    journal_title:Cells

    pub_type: 杂志文章,评审

    doi:10.3390/cells9092028

    authors: Scalise M,Console L,Rovella F,Galluccio M,Pochini L,Indiveri C

    更新日期:2020-09-03 00:00:00

  • Transcriptional Suppression of the NLRP3 Inflammasome and Cytokine Release in Primary Macrophages by Low-Dose Anthracyclines.

    abstract::Tissue-resident macrophages play critical roles in controlling homeostasis, tissue repair, and immunity. Inflammatory macrophages can sustain tissue damage and promote the development of fibrosis during infections and sterile tissue injury. The NLRP3 inflammasome and its effector cytokine IL-1β have been identified as...

    journal_title:Cells

    pub_type: 杂志文章

    doi:10.3390/cells9010079

    authors: Köse-Vogel N,Stengel S,Gardey E,Kirchberger-Tolstik T,Reuken PA,Stallmach A,Bruns T

    更新日期:2019-12-28 00:00:00

  • Novel Approaches for Identifying the Molecular Background of Schizophrenia.

    abstract::Recent advances in psychiatric genetics have led to the discovery of dozens of genomic loci associated with schizophrenia. However, a gap exists between the detection of genetic associations and understanding the underlying molecular mechanisms. This review describes the basic approaches used in the so-called post-GWA...

    journal_title:Cells

    pub_type: 杂志文章,评审

    doi:10.3390/cells9010246

    authors: Golov AK,Kondratyev NV,Kostyuk GP,Golimbet AVE

    更新日期:2020-01-18 00:00:00

  • Angiogenic Effects of Human Dental Pulp and Bone Marrow-Derived Mesenchymal Stromal Cells and their Extracellular Vesicles.

    abstract::Blood vessel formation or angiogenesis is a key process for successful tooth regeneration. Bone marrow-derived mesenchymal stromal cells (BM-MSCs) possess paracrine proangiogenic properties, which are, at least partially, induced by their extracellular vesicles (EVs). However, the isolation of BM-MSCs is associated wi...

    journal_title:Cells

    pub_type: 杂志文章

    doi:10.3390/cells9020312

    authors: Merckx G,Hosseinkhani B,Kuypers S,Deville S,Irobi J,Nelissen I,Michiels L,Lambrichts I,Bronckaers A

    更新日期:2020-01-28 00:00:00

  • Modulation of the Lipid Profile of Reconstructed Skin Substitutes after Essential Fatty Acid Supplementation Affects Testosterone Permeability.

    abstract::Skin models with efficient skin barrier function are required for percutaneous absorption studies. The contribution of media supplementation with n-3 and n-6 polyunsaturated fatty acids (PUFAs) to the development of the skin barrier function of in vitro skin models remains incompletely understood. To investigate wheth...

    journal_title:Cells

    pub_type: 杂志文章

    doi:10.3390/cells8101142

    authors: Simard M,Julien P,Fradette J,Pouliot R

    更新日期:2019-09-25 00:00:00

  • The Differences in the Proteome Profile of Cannabidiol-Treated Skin Fibroblasts following UVA or UVB Irradiation in 2D and 3D Cell Cultures.

    abstract::Cannabidiol (CBD), as the only phytocannabinoid that has no psychoactive effect, has both antioxidant and anti-inflammatory effects, and thus might be suggested as a cytoprotective compound against UV-induced metabolic changes in skin cells. Therefore, the aim of this study was to investigate the level of protective C...

    journal_title:Cells

    pub_type: 杂志文章

    doi:10.3390/cells8090995

    authors: Gęgotek A,Atalay S,Domingues P,Skrzydlewska E

    更新日期:2019-08-28 00:00:00

  • Targeting the sAC-Dependent cAMP Pool to Prevent SARS-Cov-2 Infection.

    abstract::An outbreak of the novel coronavirus (CoV) SARS-CoV-2, the causative agent of COVID-19 respiratory disease, infected millions of people since the end of 2019, led to high-level morbidity and mortality and caused worldwide social and economic disruption. There are currently no antiviral drugs available with proven effi...

    journal_title:Cells

    pub_type: 杂志文章,评审

    doi:10.3390/cells9091962

    authors: Aslam M,Ladilov Y

    更新日期:2020-08-25 00:00:00

  • Intracellular Sources of ROS/H2O2 in Health and Neurodegeneration: Spotlight on Endoplasmic Reticulum.

    abstract::Reactive oxygen species (ROS) are produced continuously throughout the cell as products of various redox reactions. Yet these products function as important signal messengers, acting through oxidation of specific target factors. Whilst excess ROS production has the potential to induce oxidative stress, physiological r...

    journal_title:Cells

    pub_type: 杂志文章,评审

    doi:10.3390/cells10020233

    authors: Konno T,Melo EP,Chambers JE,Avezov E

    更新日期:2021-01-25 00:00:00

  • The Beta3 Adrenergic Receptor in Healthy and Pathological Cardiovascular Tissues.

    abstract::The third isotype of beta-adrenoreceptors (β3-AR) has recently come (back) into focus after the observation of its expression in white and beige human adipocytes and its implication in metabolic regulation. This coincides with the recent development and marketing of agonists at the human receptor with superior specifi...

    journal_title:Cells

    pub_type: 杂志文章,评审

    doi:10.3390/cells9122584

    authors: Michel LYM,Farah C,Balligand JL

    更新日期:2020-12-02 00:00:00

  • Capillary Rarefaction in Obesity and Metabolic Diseases-Organ-Specificity and Possible Mechanisms.

    abstract::Obesity and its comorbidities like diabetes, hypertension and other cardiovascular disorders are the leading causes of death and disability worldwide. Metabolic diseases cause vascular dysfunction and loss of capillaries termed capillary rarefaction. Interestingly, obesity seems to affect capillary beds in an organ-sp...

    journal_title:Cells

    pub_type: 杂志文章,评审

    doi:10.3390/cells9122683

    authors: Paavonsalo S,Hariharan S,Lackman MH,Karaman S

    更新日期:2020-12-14 00:00:00

  • MicroRNAs in Small Extracellular Vesicles Indicate Successful Embryo Implantation during Early Pregnancy.

    abstract::Synchronous communication between the developing embryo and the receptive endometrium is crucial for embryo implantation. Thus, uterine receptivity evaluation is vital in managing recurrent implantation failure (RIF). The potential roles of small extracellular vesicle (sEV) miRNAs in pregnancy have been widely studied...

    journal_title:Cells

    pub_type: 杂志文章

    doi:10.3390/cells9030645

    authors: Tan Q,Shi S,Liang J,Zhang X,Cao D,Wang Z

    更新日期:2020-03-06 00:00:00

  • The Role of Gamma Delta T Cells in Autoimmune Rheumatic Diseases.

    abstract::Autoimmune rheumatic diseases (ARDs), affecting ~1-1.5% of all humans, are associated with considerable life long morbidity and early mortality. Early studies in the 1990s showed numerical changes of the recently discovered γδ T cells in the peripheral blood and in affected tissues of patients with a variety of ARDs, ...

    journal_title:Cells

    pub_type: 杂志文章,评审

    doi:10.3390/cells9020462

    authors: Bank I

    更新日期:2020-02-18 00:00:00

  • Nobiletin Promotes Megakaryocytic Differentiation through the MAPK/ERK-Dependent EGR1 Expression and Exerts Anti-Leukemic Effects in Human Chronic Myeloid Leukemia (CML) K562 Cells.

    abstract::Differentiation therapy is an alternative strategy used to induce the differentiation of blast cells toward mature cells and to inhibit tumor cell proliferation for cancer treatment. Nobiletin (NOB), a polymethoxyflavone phytochemical, is present abundantly in citrus peels and has been reported to possess anti-cancer ...

    journal_title:Cells

    pub_type: 杂志文章

    doi:10.3390/cells9040877

    authors: Yen JH,Lin CY,Chuang CH,Chin HK,Wu MJ,Chen PY

    更新日期:2020-04-03 00:00:00

  • Extrachromosomal Histone H2B Contributes to the Formation of the Abscission Site for Cell Division.

    abstract::Histones are constitutive components of nucleosomes and key regulators of chromatin structure. We previously observed that an extrachromosomal histone H2B (ecH2B) localizes at the intercellular bridge (ICB) connecting the two daughter cells during cytokinesis independently of DNA and RNA. Here, we show that ecH2B bind...

    journal_title:Cells

    pub_type: 杂志文章

    doi:10.3390/cells8111391

    authors: Monteonofrio L,Valente D,Rinaldo C,Soddu S

    更新日期:2019-11-05 00:00:00

  • Rebuilding Tendons: A Concise Review on the Potential of Dermal Fibroblasts.

    abstract::Tendons are vital to joint movement by connecting muscles to bones. Along with an increasing incidence of tendon injuries, tendon disorders can burden the quality of life of patients or the career of athletes. Current treatments involve surgical reconstruction and conservative therapy. Especially in the elderly popula...

    journal_title:Cells

    pub_type: 杂志文章,评审

    doi:10.3390/cells9092047

    authors: Chu J,Lu M,Pfeifer CG,Alt V,Docheva D

    更新日期:2020-09-08 00:00:00

  • Hypothermia Advocates Functional Mitochondria and Alleviates Oxidative Stress to Combat Acetaminophen-Induced Hepatotoxicity.

    abstract::For years, moderate hypothermia (32 °C) has been proposed as an unorthodox therapy for liver injuries, with proven hepatoprotective potential. Yet, limited mechanistic understanding has largely denied its acceptance over conventional pharmaceuticals for hepatoprotection. Today, facing a high prevalence of acetaminophe...

    journal_title:Cells

    pub_type: 杂志文章

    doi:10.3390/cells9112354

    authors: Tan YL,Ho HK

    更新日期:2020-10-26 00:00:00

  • Role of Notch Receptors in Hematologic Malignancies.

    abstract::Notch receptors are single-pass transmembrane proteins that play a critical role in cell fate decisions and have been implicated in the regulation of many developmental processes. The human Notch family comprises of four receptors (Notch 1 to 4) and five ligands. Their signaling can regulate extremely basic cellular p...

    journal_title:Cells

    pub_type: 杂志文章,评审

    doi:10.3390/cells10010016

    authors: Gragnani L,Lorini S,Marri S,Zignego AL

    更新日期:2020-12-24 00:00:00

  • Differential Effects of Extracellular Vesicles of Lineage-Specific Human Pluripotent Stem Cells on the Cellular Behaviors of Isogenic Cortical Spheroids.

    abstract::Extracellular vesicles (EVs) contribute to a variety of signaling processes and the overall physiological and pathological states of stem cells and tissues. Human induced pluripotent stem cells (hiPSCs) have unique characteristics that can mimic embryonic tissue development. There is growing interest in the use of EVs...

    journal_title:Cells

    pub_type: 杂志文章

    doi:10.3390/cells8090993

    authors: Marzano M,Bejoy J,Cheerathodi MR,Sun L,York SB,Zhao J,Kanekiyo T,Bu G,Meckes DG Jr,Li Y

    更新日期:2019-08-28 00:00:00

  • Inhibition of Transglutaminase 2 but Not of MDM2 Has a Significant Therapeutic Effect on Renal Cell Carcinoma.

    abstract::More than 50% of human cancers harbor TP53 mutations and increased expression of Mouse double minute 2 homolog(MDM2), which contribute to cancer progression and drug resistance. Renal cell carcinoma (RCC) has an unusually high incidence of wild-type p53, with a mutation rate of less than 4%. MDM2 is master regulator o...

    journal_title:Cells

    pub_type: 杂志文章

    doi:10.3390/cells9061475

    authors: Kang JH,Lee SH,Lee JS,Oh SJ,Ha JS,Choi HJ,Kim SY

    更新日期:2020-06-16 00:00:00

  • The Transcription Factor EB Reduces the Intraneuronal Accumulation of the Beta-Secretase-Derived APP Fragment C99 in Cellular and Mouse Alzheimer’s Disease Models.

    abstract::: Brains that are affected by Alzheimer's disease (AD) are characterized by the overload of extracellular amyloid β (Aβ) peptides, but recent data from cellular and animal models propose that Aβ deposition is preceded by intraneuronal accumulation of the direct precursor of Aβ, C99. These studies indicate that C99 acc...

    journal_title:Cells

    pub_type: 杂志文章

    doi:10.3390/cells9051204

    authors: Bécot A,Pardossi-Piquard R,Bourgeois A,Duplan E,Xiao Q,Diwan A,Lee JM,Lauritzen I,Checler F

    更新日期:2020-05-12 00:00:00

  • Cytokine Directed Chondroblast Trans-Differentiation: JAK Inhibition Facilitates Direct Reprogramming of Fibroblasts to Chondroblasts.

    abstract::Osteoarthritis (OA) is a degenerative disease of the hyaline articular cartilage. This disease is progressive and may lead to disability. Researchers proposed many regenerative approaches to treat osteoarthritis, including stem cells. Trans-differentiation of a fully differentiated cell state directly into another dif...

    journal_title:Cells

    pub_type: 杂志文章

    doi:10.3390/cells9010191

    authors: Cota P,Helmi SA,Hsu C,Rancourt DE

    更新日期:2020-01-11 00:00:00

  • The Snapdragon LATE ELONGATED HYPOCOTYL Plays A Dual Role in Activating Floral Growth and Scent Emission.

    abstract::The plant circadian clock controls a large number of internal processes, including growth and metabolism. Scent emission displays a circadian pattern in many species such as the snapdragon. Here we show that knocking down LATE ELONGATED HYPOCOTYL in Antirrhinum majus affects growth and scent emission. In order to gain...

    journal_title:Cells

    pub_type: 杂志文章

    doi:10.3390/cells8080920

    authors: Terry MI,Pérez-Sanz F,Navarro PJ,Weiss J,Egea-Cortines M

    更新日期:2019-08-17 00:00:00

  • Multidisciplinary Roles of LRRFIP1/GCF2 in Human Biological Systems and Diseases.

    abstract::Leucine Rich Repeat of Flightless-1 Interacting Protein 1/GC-binding factor 2 (LRRFIP1/GCF2) cDNA was cloned for a transcriptional repressor GCF2, which bound sequence-specifically to a GC-rich element of epidermal growth factor receptor (EGFR) gene and repressed its promotor. LRRFIP1/GCF2 was also cloned as a double ...

    journal_title:Cells

    pub_type: 杂志文章,评审

    doi:10.3390/cells8020108

    authors: Takimoto M

    更新日期:2019-01-31 00:00:00

  • PDPN Is Expressed in Various Types of Canine Tumors and Its Silencing Induces Apoptosis and Cell Cycle Arrest in Canine Malignant Melanoma.

    abstract::Podoplanin (PDPN), a small transmembrane mucin-like glycoprotein, is ectopically expressed. It is also known to be linked with several aspects of tumor malignancy in some types of human tumors, including invasion, metastasis, and cancer stemness. However, there are few reports on the expression of dog PDPN (dPDPN) in ...

    journal_title:Cells

    pub_type: 杂志文章

    doi:10.3390/cells9051136

    authors: Shinada M,Kato D,Kamoto S,Yoshimoto S,Tsuboi M,Yoshitake R,Eto S,Ikeda N,Saeki K,Hashimoto Y,Takahashi Y,Chambers J,Uchida K,Kaneko MK,Fujita N,Nishimura R,Kato Y,Nakagawa T

    更新日期:2020-05-05 00:00:00

  • Circulating Platelet-Derived Extracellular Vesicles Are a Hallmark of Sars-Cov-2 Infection.

    abstract::Sars-Cov-2 infection causes fever and cough that may rapidly lead to acute respiratory distress syndrome (ARDS). Few biomarkers have been identified but, unfortunately, these are individually poorly specific, and novel biomarkers are needed to better predict patient outcome. The aim of this study was to evaluate the d...

    journal_title:Cells

    pub_type: 杂志文章

    doi:10.3390/cells10010085

    authors: Cappellano G,Raineri D,Rolla R,Giordano M,Puricelli C,Vilardo B,Manfredi M,Cantaluppi V,Sainaghi PP,Castello L,De Vita N,Scotti L,Vaschetto R,Dianzani U,Chiocchetti A

    更新日期:2021-01-07 00:00:00

  • Novel Insights into Beta 2 Adrenergic Receptor Function in the rd10 Model of Retinitis Pigmentosa.

    abstract::Background: In retinitis pigmentosa (RP), inherited rod death is followed by cone loss and blindness. Why cones die is still a matter of consideration. Here, we investigate the pathogenic role of the sympathetic transmission in the rd10 mouse model of RP. Methods: Retinal levels of beta adrenergic receptor (BAR) 2 and...

    journal_title:Cells

    pub_type: 杂志文章

    doi:10.3390/cells9092060

    authors: Cammalleri M,Dal Monte M,Amato R,Lapi D,Bagnoli P

    更新日期:2020-09-09 00:00:00

  • Anti-Cytokine Autoantibodies in Systemic Lupus Erythematosus.

    abstract::Cytokine dysregulation is characteristic of systemic lupus erythematosus (SLE), a systemic autoimmune disease of considerable heterogeneity. Insights gained about the cytokine dysregulation in SLE have the potential for identifying patient subsets before the onset of clinical disease and during established disease. Cl...

    journal_title:Cells

    pub_type: 杂志文章,评审

    doi:10.3390/cells9010072

    authors: Howe HS,Leung BPL

    更新日期:2019-12-27 00:00:00

  • The Diverse Roles of TIMP-3: Insights into Degenerative Diseases of the Senescent Retina and Brain.

    abstract::Tissue inhibitor of metalloproteinase-3 (TIMP-3) is a component of the extracellular environment, where it mediates diverse processes including matrix regulation/turnover, inflammation and angiogenesis. Rare TIMP-3 risk alleles and mutations are directly linked with retinopathies such as age-related macular degenerati...

    journal_title:Cells

    pub_type: 杂志文章,评审

    doi:10.3390/cells9010039

    authors: Dewing JM,Carare RO,Lotery AJ,Ratnayaka JA

    更新日期:2019-12-21 00:00:00

  • Automated Counting of Cancer Cells by Ensembling Deep Features.

    abstract::High-content and high-throughput digital microscopes have generated large image sets in biological experiments and clinical practice. Automatic image analysis techniques, such as cell counting, are in high demand. Here, cell counting was treated as a regression problem using image features (phenotypes) extracted by de...

    journal_title:Cells

    pub_type: 杂志文章

    doi:10.3390/cells8091019

    authors: Liu Q,Junker A,Murakami K,Hu P

    更新日期:2019-09-02 00:00:00

  • Noninvasive Diagnosis of NAFLD and NASH.

    abstract::The aim of this review is to outline emerging biomarkers that can serve as early diagnostic tools to identify patients with nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) and, among them, the subgroup of best candidates for clinical trials on emerging compounds. Regarding possible pre...

    journal_title:Cells

    pub_type: 杂志文章,评审

    doi:10.3390/cells9041005

    authors: Piazzolla VA,Mangia A

    更新日期:2020-04-17 00:00:00