OBJECTIVE: To investigate the role of DYRK1A in the cytarabine (Ara-C) resistance mechanism of acute myeloid leukemia (AML) cells. METHODS: Overexpression and silencing of DYRK1A gene in THP-1 cells were used to observe whether the sensitivity of THP-1 cells to Ara-C was altered. RT-PCR was used to detect the changes in mRNA expression of related genes during Ara-C transport or metabolism. Western blot and RT-PCR were used to detect SAMHD1 expression after regulating DYRK1A expression in Ara-C treated cells. Co-IP technology was used to detect the interaction between Cyclin L2, DYRK1A, and SAMHD1. RESULTS: Overexpression of DYRK1A decreased Ara-C sensitivity in THP-1 cells while silencing DYRK1A increased it. Overexpression and silencing of DYRK1A did not affect Ara-C transport or metabolic gene expression. Overexpression of DYRK1A could increase the expression of SAMHD1 protein in cells, while silencing DYRK1A reduced SAMHD1 expression. Cyclin L2 interacted with DYRK1A and SAMHD1 in THP-1 cells. CONCLUSION DYRK1A is involved in Ara-C resistance in AML cells, and its mechanism may be related to increased expression of SAMHD1 by interacting with Cyclin L2.
Humans ; Cytarabine/pharmacology* ; Protein-Tyrosine Kinases/metabolism* ; Leukemia, Myeloid, Acute ; Dyrk Kinases ; Drug Resistance, Neoplasm ; Protein Serine-Threonine Kinases/metabolism* ; SAM Domain and HD Domain-Containing Protein 1 ; Cell Line, Tumor

Human monocyte is an important cell type which is involved in various complex human diseases. To better understand the biology of human monocytes and facilitate further studies, we developed the first comprehensive proteome knowledge base specifically for human monocytes by integrating both in vivo and in vitro datasets. The top 2000 expressed genes from in vitro datasets and 779 genes from in vivo experiments were integrated into this study. Altogether, a total of 2237 unique monocyte-expressed genes were cataloged. Biological functions of these monocyte-expressed genes were annotated and classified via Gene Ontology (GO) analysis. Furthermore, by extracting the overlapped genes from in vivo and in vitro datasets, a core gene list including 541 unique genes was generated. Based on the core gene list, further gene-disease associations, pathway and network analyses were performed. Data analyses based on multiple bioinformatics tools produced a large body of biologically meaningful information, and revealed a number of genes such as SAMHD1, G6PD, GPD2 and ENO1, which have been reported to be related to immune response, blood biology, bone remodeling, and cancer respectively. As a unique resource, this study can serve as a reference map for future in-depth research on monocytes biology and monocyte-involved human diseases.
Aged ; Biomarkers, Tumor ; metabolism ; DNA-Binding Proteins ; metabolism ; Female ; Glucosephosphate Dehydrogenase ; metabolism ; Humans ; Mass Spectrometry ; methods ; Middle Aged ; Monocytes ; metabolism ; Monomeric GTP-Binding Proteins ; metabolism ; Phosphopyruvate Hydratase ; metabolism ; Proteomics ; methods ; SAM Domain and HD Domain-Containing Protein 1 ; Tumor Suppressor Proteins ; metabolism

OBJECTIVETo review the mechanisms by which HIV evades different components of the host immune system.

DATA SOURCESThis review is based on data obtained from published articles from 1991 to 2012. To perform the PubMed literature search, the following key words were input: HIV and immune evasion.

STUDY SELECTIONArticles containing information related to HIV immune evasion were selected.

RESULTSAlthough HIV is able to induce vigorous antiviral immune responses, viral replication cannot be fully controlled, and neither pre-existing infected cells nor latent HIV infection can be completely eradicated. Like many other enveloped viruses, HIV can escape recognition by the innate and adaptive immune systems. Recent findings have demonstrated that HIV can also successfully evade host restriction factors, the components of intrinsic immune system, such as APOBEC3G (apolipoprotein B mRNA-editing enzyme, catalytic polypeptide-like 3G), TRIM5α (tripartite motif 5-α), tetherin, and SAMHD1 (SAM-domain HD-domain containing protein).

CONCLUSIONSHIV immune evasion plays an important role in HIV pathogenesis. Fully understanding the tactics deployed by HIV to evade various components of the host immune systems will allow for the development of novel strategies aimed toward the prevention and cure of HIV/AIDS.

APOBEC-3G Deaminase ; Adaptive Immunity ; Antibodies, Neutralizing ; immunology ; Antigens, CD ; physiology ; Carrier Proteins ; physiology ; Complement System Proteins ; immunology ; Cytidine Deaminase ; physiology ; GPI-Linked Proteins ; physiology ; HIV-1 ; immunology ; Humans ; Immune Evasion ; Killer Cells, Natural ; immunology ; Monomeric GTP-Binding Proteins ; physiology ; SAM Domain and HD Domain-Containing Protein 1

The SAM and HD domain containing protein 1 (Sterile alpha motif domain and HD domain-containing protein 1, SAMHD1) is a putative negative regulator of the antiviral innate immune response. It can significantly increase the antiviral immune response, mediates the interferon-induced inflammatory response involved in the host foreign-virus defense system. The early studies have focused on its gene mutations associated with Aicardi-Goutières syndrome (AGS), the latest study found that SAMHD1 as a potent dGTP-stimulated triphosphohydrolase restricts HIV-1 replication by hydrolyzing the majority of cellular dNTPs, thus inhibiting reverse transcription and viral complementary DNA (cDNA) synthesis. Auxiliary gene of HIV-2 and simian immunodeficiency virus (SIVsm / mac) encoding the Vpx protein can eliminate HIV-1 restriction. In recent years, the research on SAMHD1, mores forward rapidly this paper overviews the recent research progression related to the above fields.
Animals ; Cell Line ; HIV ; metabolism ; physiology ; Humans ; Monomeric GTP-Binding Proteins ; genetics ; metabolism ; SAM Domain and HD Domain-Containing Protein 1 ; Viral Regulatory and Accessory Proteins ; metabolism