Unlocking the power of Zc3h12c: Orchestrating Macrophage activation and elevating the innate immune response.

The activation of macrophages, essential for the innate defense against invading pathogens, revolves around Toll-like receptors (TLRs). Nevertheless, a comprehensive understanding of the molecular mechanisms governing TLR signaling in the course of macrophage activation remains to be fully clarified. Although Zc3h12c was originally identified as being enriched in organs associated with macrophages, its precise function remains elusive.

Self-programmed dynamics of T cell receptor condensation.

A common event upon receptor-ligand engagement is the formation of receptor clusters on the cell surface, in which signaling molecules are specifically recruited or excluded to form signaling hubs to regulate cellular events. These clusters are often transient and can be disassembled to terminate signaling. Despite the general relevance of dynamic receptor clustering in cell signaling, the regulatory mechanism underlying the dynamics is still poorly understood.

DNMT3A Mutation-Induced CDK1 Overexpression Promotes Leukemogenesis by Modulating the Interaction between EZH2 and DNMT3A.

mutations are frequently identified in acute myeloid leukemia (AML) and indicate poor prognosis. Previously, we found that the hotspot mutation DNMT3A R882H could upregulate CDK1 and induce AML in conditional knock-in mice. However, the mechanism by which CDK1 is involved in leukemogenesis of DNMT3A mutation-related AML, and whether CDK1 could be a therapeutic target, remains unclear.

Identification of a Long Noncoding RNA as Key Regulator of IL-17 Signaling through the SRSF10-IRF1-Act1 Axis in Autoimmune Diseases.

IL-17A plays an essential role in the pathogenesis of many autoimmune diseases, including psoriasis and multiple sclerosis. Act1 is a critical adaptor in the IL-17A signaling pathway. In this study, we report that an anti-sense long noncoding RNA, , regulates Act1 expression and IL-17A signaling by recruiting SRSF10, which downregulates the expression of IRF1, a transcriptional factor of Act1.

RIG-I regulates myeloid differentiation by promoting TRIM25-mediated ISGylation.

Retinoic acid-inducible gene I (RIG-I) is up-regulated during granulocytic differentiation of acute promyelocytic leukemia (APL) cells induced by all- retinoic acid (ATRA). It has been reported that RIG-I recognizes virus-specific 5'-ppp-double-stranded RNA (dsRNA) and activates the type I interferons signaling pathways in innate immunity. However, the functions of RIG-I in hematopoiesis remain unclear, especially regarding its possible interaction with endogenous RNAs and the associated pathways that could contribute to the cellular differentiation and maturation.

Cooperation of Dnmt3a R878H with Nras G12D promotes leukemogenesis in knock-in mice: a pilot study.

Background: DNMT3A R882H, a frequent mutation in acute myeloid leukemia (AML), plays a critical role in malignant hematopoiesis. Recent findings suggest that DNMT3A mutant acts as a founder mutation and requires additional genetic events to induce full-blown AML. Here, we investigated the cooperation of mutant DNMT3A and NRAS in leukemogenesis by generating a double knock-in (DKI) mouse model harboring both Dnmt3a R878H and Nras G12D mutations.

Homoharringtonine deregulates transcriptional expression by directly binding NF-κB repressing factor.

Homoharringtonine (HHT), a known protein synthesis inhibitor, has an anti-myeloid leukemia effect and potentiates the therapeutic efficacy of anthracycline/cytarabine induction regimens for acute myelogenous leukemia (AML) with favorable and intermediate prognoses, especially in the t(8;21) subtype. Here we provide evidence showing that HHT inhibits the activity of leukemia-initiating cells (Lin/Sca-1/c-kit; LICs) in a t(8;21) murine leukemia model and exerts a down-regulating effect on MYC pathway genes in human t(8;21) leukemia cells (Kasumi-1). We discovered that NF-κB repressing factor (NKRF) is bound directly by HHT via the second double-strand RNA-binding motif (DSRM2) domain, which is the nuclear localization signal of NKRF.

Conditional knockin of Dnmt3a R878H initiates acute myeloid leukemia with mTOR pathway involvement.

is frequently mutated in acute myeloid leukemia (AML). To explore the features of human AML with the hotspot R882H mutation, we generated Dnmt3a R878H conditional knockin mice, which developed AML with enlarged LinSca1cKit cell compartments. The transcriptome and DNA methylation profiling of bulk leukemic cells and the single-cell RNA sequencing of leukemic stem/progenitor cells revealed significant changes in gene expression and epigenetic regulatory patterns that cause differentiation arrest and growth advantage.

Herpes Simplex Virus 1 Induces Phosphorylation and Reorganization of Lamin A/C through the γ134.5 Protein That Facilitates Nuclear Egress.

Unlabelled: Herpes simplex virus 1 (HSV-1) remodels nuclear membranes during virus egress. Although the UL31 and UL34 proteins control nucleocapsid transit in infected cells, the molecular interactions required for their function are unclear. Here we report that the γ34.

Systematic identification of arsenic-binding proteins reveals that hexokinase-2 is inhibited by arsenic.

Arsenic is highly effective for treating acute promyelocytic leukemia (APL) and has shown significant promise against many other tumors. However, although its mechanistic effects in APL are established, its broader anticancer mode of action is not understood. In this study, using a human proteome microarray, we identified 360 proteins that specifically bind arsenic.

The Us3 Protein of Herpes Simplex Virus 1 Inhibits T Cell Signaling by Confining Linker for Activation of T Cells (LAT) Activation via TRAF6 Protein.

Herpes simplex virus 1 (HSV-1) is the most prevalent human virus and causes global morbidity because the virus is able to infect multiple cell types. Remarkably, HSV infection switches between lytic and latent cycles, where T cells play a critical role. However, the precise way of virus-host interactions is incompletely understood.

p32 is a novel target for viral protein ICP34.5 of herpes simplex virus type 1 and facilitates viral nuclear egress.

As a large double-stranded DNA virus, herpes simplex virus type 1 (HSV-1) assembles capsids in the nucleus where the viral particles exit by budding through the inner nuclear membrane. Although a number of viral and host proteins are involved, the machinery of viral egress is not well understood. In a search for host interacting proteins of ICP34.

Prognostic significance of 2-hydroxyglutarate levels in acute myeloid leukemia in China.

The 2-hydroxyglutarate (2-HG) has been reported to result from mutations of isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) genes and to function as an "oncometabolite." To evaluate the clinical significance of serum 2-HG levels in hematologic malignancies, acute myeloid leukemia (AML) in particular, we analyzed this metabolite in distinct types of human leukemia and lymphoma and established the range of serum 2-HG in appropriate normal control individuals by using gas chromatograph-time-of-flight mass spectrometry. Aberrant serum 2-HG pattern was detected in the multicenter group of AML, with 62 of 367 (17%) patients having 2-HG levels above the cutoff value (2.

Rapid diagnosis and prognosis of de novo acute myeloid leukemia by serum metabonomic analysis.

Acute myeloid leukemia (AML) is a life-threatening hematological disease. Novel diagnostic and prognostic markers will be essential for new therapeutics and for significantly improving the disease prognosis. To characterize the metabolic features associated with AML and search for potential diagnostic and prognostic methods, here we analyzed the phenotypic characteristics of serum metabolite composition (metabonome) in a cohort of 183 patients with de novo acute myeloid leukemia together with 232 age- and gender-matched healthy controls using (1)H NMR spectroscopy in conjunction with multivariate data analysis.

Dual roles of PKM2 in cancer metabolism.

Cancer cells have distinct metabolism that highly depends on glycolysis instead of mitochondrial oxidative phosphorylation alone, known as aerobic glycolysis. Pyruvate kinase (PK), which catalyzes the final step of glycolysis, has emerged as a potential regulator of this metabolic phenotype. Expression of PK type M2 (PKM2) is increased and facilitates lactate production in cancer cells, which determines whether the glucose carbons are degraded to pyruvate and lactate or are channeled into synthetic processes.