Showing 1-30 of 238 results for "

H7904

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Harri M Itkonen et al.
Theranostics, 9(8), 2183-2197 (2019-06-01)
O-GlcNAc transferase (OGT) is overexpressed in aggressive prostate cancer. OGT modifies intra-cellular proteins via single sugar conjugation (O-GlcNAcylation) to alter their activity. We recently discovered the first fast-acting OGT inhibitor OSMI-2. Here, we probe the stability and function of the...
Mekayla A Storer et al.
Developmental cell, 52(4), 509-524 (2020-01-07)
Here, we investigate the origin and nature of blastema cells that regenerate the adult murine digit tip. We show that Pdgfra-expressing mesenchymal cells in uninjured digits establish the regenerative blastema and are essential for regeneration. Single-cell profiling shows that the...
C C Zhang et al.
The Journal of biological chemistry, 275(1), 479-486 (2000-01-05)
17beta-Estradiol (E(2)) or the antiestrogen, 4-hydroxytamoxifen (OHT), induce apoptosis in stably transfected estrogen receptor (ER)-positive HeLa-ER5 cells. p38 mitogen-activated protein kinase is implicated in cellular processes involving apoptosis. The p38 kinase inhibitor, SB203580, partially protects HeLa-ER5 cells against apoptosis induced...
Federico Galvagni et al.
Stem cells (Dayton, Ohio), 33(3), 742-750 (2014-12-17)
Although much is known about the pluripotency self-renewal circuitry, the molecular events that lead embryonic stem cells (ESCs) exit from pluripotency and begin differentiation are largely unknown. We found that the zinc finger transcription factor Snai1, involved in gastrulation and...
Melissa Crawford et al.
Molecular biology of the cell, 31(8), 768-781 (2020-02-13)
Melanosomes are melanin-containing organelles that provide pigmentation and protection from solar UV radiation to the skin. In melanocytes, melanosomes mature and traffic to dendritic tips, where they are transferred to adjacent epidermal keratinocytes through pathways that involve microtubule networks and...
Davood Sabour et al.
PloS one, 9(8), e103985-e103985 (2014-08-21)
Expression of germ cell nuclear factor (GCNF; Nr6a1), an orphan member of the nuclear receptor gene family of transcription factors, during gastrulation and neurulation is critical for normal embryogenesis in mice. Gcnf represses the expression of the POU-domain transcription factor...
Timothy Marsh et al.
Developmental cell, 52(5), 591-604 (2020-02-23)
Although autophagy is being pursued as a therapeutic target in clinical oncology trials, its effects on metastasis, the principal cause of cancer mortality, remain unclear. Here, we utilize mammary cancer models to temporally delete essential autophagy regulators during carcinoma progression....
Rui Guo et al.
Molecular cell, 78(4), 653-669 (2020-04-22)
Epstein-Barr virus (EBV) is associated with multiple human malignancies. To evade immune detection, EBV switches between latent and lytic programs. How viral latency is maintained in tumors or in memory B cells, the reservoir for lifelong EBV infection, remains incompletely...
Mai Sato et al.
The Journal of cell biology, 220(2) (2021-01-07)
Cancer cells develop strong genetic dependencies, enabling survival under oncogenic stress. MYC is a key oncogene activated across most cancers, and identifying associated synthetic lethality or sickness can provide important clues about its activity and potential therapeutic strategies. On the...
Sarah A Scott et al.
Nature chemical biology, 5(2), 108-117 (2009-01-13)
Phospholipase D (PLD) is an essential enzyme responsible for the production of the lipid second messenger phosphatidic acid. Phosphatidic acid participates in both G protein-coupled receptor and receptor tyrosine kinase signal transduction networks. The lack of potent and isoform-selective inhibitors...
Marcus Conrad et al.
Proceedings of the National Academy of Sciences of the United States of America, 107(36), 15774-15779 (2010-08-28)
Protein tyrosine phosphatases (PTPs) are regulated through reversible oxidation of the active-site cysteine. Previous studies have implied soluble reactive oxygen species (ROS), like H(2)O(2), as the mediators of PTP oxidation. The potential role(s) of peroxidized lipids in PTP oxidation have...
Yi Zhang et al.
Nature communications, 10(1), 2314-2314 (2019-05-28)
Histone methyltransferase MLL4 is centrally involved in transcriptional regulation and is often mutated in human diseases, including cancer and developmental disorders. MLL4 contains a catalytic SET domain that mono-methylates histone H3K4 and seven PHD fingers of unclear function. Here, we...
Veena Padmanaban et al.
Nature, 573(7774), 439-444 (2019-09-06)
Metastasis is the major driver of death in patients with cancer. Invasion of surrounding tissues and metastasis have been proposed to initiate following loss of the intercellular adhesion protein, E-cadherin1,2, on the basis of inverse correlations between in vitro migration...
Christian Henninger et al.
Biochemical pharmacology, 164, 82-93 (2019-04-03)
Cardiotoxicity is the dose limiting adverse effect of anthracycline-based anticancer therapy. Inhibitor studies point to Rac1 as therapeutic target to prevent anthracycline-induced cardiotoxicity. Yet, supporting genetic evidence is still missing and the pathophysiological relevance of different cardiac cell types is...
Nowsheen Mullani et al.
Life science alliance, 4(3) (2021-01-16)
Accumulation of senescent cells is an important contributor to chronic inflammation upon aging. The inflammatory phenotype of senescent cells was previously shown to be driven by cytoplasmic DNA. Here, we propose that cytoplasmic double-stranded RNA has a similar effect. We...
Abhijeet Sharma et al.
Proceedings of the National Academy of Sciences of the United States of America, 116(43), 21800-21811 (2019-10-09)
The excitatory amino acid transporter 2 (EAAT2) is the major glutamate transporter in the brain expressed predominantly in astrocytes and at low levels in neurons and axonal terminals. EAAT2 expression is reduced in aging and sporadic Alzheimer's disease (AD) patients'...
Liang Wei Wang et al.
Cell metabolism, 30(3), 539-555 (2019-07-02)
Epstein-Barr virus (EBV) causes Burkitt, Hodgkin, and post-transplant B cell lymphomas. How EBV remodels metabolic pathways to support rapid B cell outgrowth remains largely unknown. To gain insights, primary human B cells were profiled by tandem-mass-tag-based proteomics at rest and...
Kevin M Davis et al.
Nature chemical biology, 11(5), 316-318 (2015-04-08)
Directly modulating the activity of genome-editing proteins has the potential to increase their specificity by reducing activity following target locus modification. We developed Cas9 nucleases that are activated by the presence of a cell-permeable small molecule by inserting an evolved...
Priscilla Cheung et al.
Cell stem cell, 27(4), 590-604 (2020-07-31)
Although the Hippo transcriptional coactivator YAP is considered oncogenic in many tissues, its roles in intestinal homeostasis and colorectal cancer (CRC) remain controversial. Here, we demonstrate that the Hippo kinases LATS1/2 and MST1/2, which inhibit YAP activity, are required for...
Salome Stierli et al.
Development (Cambridge, England), 145(24) (2018-11-11)
Peripheral nerves are highly regenerative, in contrast to the poor regenerative capabilities of the central nervous system (CNS). Here, we show that adult peripheral nerve is a more quiescent tissue than the CNS, yet all cell types within a peripheral...
Akira Imamoto et al.
Life science alliance, 3(2) (2020-02-12)
CRK and CRKL (CRK-like) encode adapter proteins with similar biochemical properties. Here, we show that a 50% reduction of the family-combined dosage generates developmental defects, including aspects of DiGeorge/del22q11 syndrome in mice. Like the mouse homologs of two 22q11.21 genes...
Bo-Ran Choi et al.
Cell reports, 31(5), 107540-107540 (2020-05-07)
Neurons and oligodendrocytes communicate to regulate oligodendrocyte development and ensure appropriate axonal myelination. Here, we show that Glycerophosphodiester phosphodiesterase 2 (GDE2) signaling underlies a neuronal pathway that promotes oligodendrocyte maturation through the release of soluble neuronally derived factors. Mice lacking...
Simon D Schwarz et al.
F1000Research, 9, 1112-1112 (2020-11-05)
Mechanistic and functional studies by gene disruption or editing approaches often suffer from confounding effects like compensatory cellular adaptations generated by clonal selection. These issues become particularly relevant when studying factors directly involved in genetic or epigenetic maintenance. To provide...
Andrea Repele et al.
PloS one, 14(6), e0217580-e0217580 (2019-06-11)
Cebpa encodes a transcription factor (TF) that plays an instructive role in the development of multiple myeloid lineages. The expression of Cebpa itself is finely modulated, as Cebpa is expressed at high and intermediate levels in neutrophils and macrophages respectively...
Annemarie E M Post et al.
Oncology research, 28(1), 33-40 (2019-05-03)
Tamoxifen-induced radioresistance, reported in vitro, might pose a problem for patients who receive neoadjuvant tamoxifen treatment and subsequently receive radiotherapy after surgery. Previous studies suggested that DNA damage repair or cell cycle genes are involved, and could therefore be targeted...
Dale O Cowley et al.
Molecular and cellular biology, 29(4), 1059-1071 (2008-12-17)
Aurora-A is a conserved kinase implicated in mitotic regulation and carcinogenesis. Aurora-A was previously implicated in mitotic entry and spindle assembly, although contradictory results prevented a clear understanding of the roles of Aurora-A in mammals. We developed a conditional null...
Samantha Kent et al.
Cell reports, 33(2), 108248-108248 (2020-10-15)
Compartmentalization by liquid-liquid phase separation is implicated in transcription. It remains unclear whether and how transcriptional condensates accelerate the search of transcriptional regulatory factors for their target sites. Furthermore, the molecular mechanisms by which regulatory factors nucleate on chromatin to...
Sara Nicolai et al.
Oncogene, 39(4), 754-766 (2019-10-02)
Efficient repair of DNA double-strand breaks (DSBs) is of critical importance for cell survival. Although non-homologous end joining (NHEJ) is the most used DSBs repair pathway in the cells, how NHEJ factors are sequentially recruited to damaged chromatin remains unclear....
Susan E Leggett et al.
Proceedings of the National Academy of Sciences of the United States of America, 117(11), 5655-5663 (2020-03-04)
Epithelial tissues mechanically deform the surrounding extracellular matrix during embryonic development, wound repair, and tumor invasion. Ex vivo measurements of such multicellular tractions within three-dimensional (3D) biomaterials could elucidate collective dissemination during disease progression and enable preclinical testing of targeted...
Shuting Wu et al.
Science advances, 6(47) (2020-11-20)
Microglia are the tissue-resident macrophages in the central nervous system and are critically involved in immune defense, neural development and function, and neuroinflammation. The versatility of microglia has long been attributed to heterogeneity. Recent studies have revealed possible heterogeneity in...