Domain Structure of Human Nuclear DNA Helicase II (RNA Helicase A)

Zhang, Suisheng; Grosse, Frank

doi:10.1074/jbc.272.17.11487

Cited by 110 publications

(128 citation statements)

References 42 publications

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“…29 -32 In addition to these genes, many important regulators of cell cyclerelated events including centrosome separation/segregation (eg, ARK2), 33 kinetochore association (eg, CENF), 34 functional components of mitotic check points (eg, CENPE and TTK orMps1), 35,36 chromatin association and DNA replication (eg, HMG-I/Y, chromatin assembly factor-I (p150), DNA helicase and DHFR). [37][38][39] A group of genes that promotes G 2 /M transit or are expressed in the M phase of the cell cycle, including CYCLIN-A, CDC2, CDC25C, and SAK, 40 -42 were also up-regulated. These results suggest that t(14;18)-negative GCB-DLBCL is significantly more mitotically active than the t(14;18)-positive cases, and indicates that the two cytogenetic subsets have distinctive biological characteristics.…”

Section: Discussionmentioning

confidence: 99%

BCL2 Translocation Defines a Unique Tumor Subset within the Germinal Center B-Cell-Like Diffuse Large B-Cell Lymphoma

Iqbal

Sanger

Horsman

et al. 2004

The American Journal of Pathology

267

173

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Gene expression profiling of diffuse large B-cell lymphoma (DLBCL) has revealed prognostically important subgroups: germinal center B-cell-like (GCB) DL-BCL, activated B cell-like (ABC) DLBCL, and primary mediastinal large B-cell lymphoma. The t(14;18)(q32; q21) has been reported previously to define a unique subset within the GCB-DLBCL. We evaluated for the translocation in 141 cases of DLBCL that were successfully gene expression profiled. Using a dual-probe fluorescence in situ hybridization assay, we detected the t(14;18) in 17% of DLBCLs and in 34% of the GCB subgroup which contained the vast majority of positive cases. In addition, 12 t(14;18)-positive cases detected by polymerase chain reaction assays on additional samples were added to the fluorescence in situ hybridization-positive cases for subsequent analysis. Immunohistochemical data indicated that BCL2, BCL6, and CD10 protein were preferentially expressed in the t(14;18)-positive cases as compared to t(14;18)-negative cases. Within the GCB subgroup, the expression of BCL2 and CD10, but not BCL6, differed significantly between cases with or without the t(14; 18): 88% versus 24% for BCL2 and 72% versus 32% for CD10, respectively. In the GCB-DLBCL subgroup, a heterogeneous group of genes is overexpressed in the t(14;18)-positive subset, among which BCL2 is a significant discriminator. Interestingly, the t(14;18)-negative subset is dominated by overexpression of cell cycle-associated genes, indicating that these tumors are significantly more proliferative, suggesting distinctive pathogenetic mechanisms. However, despite this higher proliferative activity, there was no significant difference in overall or failure-free survival between the t(14;18)-positive and -negative subsets within the GCB subgroup. Diffuse large B-cell lymphoma (DLBCL) is an aggressive malignancy of mature B cells with an annual incidence of ϳ25,000 cases in the United States. DLBCL is a heterogeneous entity both clinically and morphologically. We have recently shown by gene expression profiling that DLBCL can be classified into two major subgroups. 1 The germinal center B-cell-like (GCB) subgroup expresses genes characteristic of normal GC B cells and is associated with a good outcome after multiagent chemotherapy, whereas the activated B-cell-like (ABC) subgroup expresses genes characteristic of activated blood B cells and is associated with a poor clinical outcome. Nonetheless, considerable molecular heterogeneity exists within each subgroup. A small number of DLBCL cases are unclassifiable and do not express the GCB or ABC sig-

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Section: Discussionmentioning

confidence: 99%

BCL2 Translocation Defines a Unique Tumor Subset within the Germinal Center B-Cell-Like Diffuse Large B-Cell Lymphoma

Iqbal

Sanger

Horsman

et al. 2004

The American Journal of Pathology

267

173

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“…DNA-PK purified from human cells was purchased from Promega (Madison, WI). Full-length human NDH II (amino acids 1-1269) and its deletion versions comprising amino acids 1-952, 313-1269, and 313-952 were generated in our laboratory and have been described previously (24). All of these NDH II recombinant proteins carried His 6 tags at their N termini and were expressed from recombinant baculoviruses in Sf9 insect cells.…”

Section: Methodsmentioning

confidence: 99%

“…All of these NDH II recombinant proteins carried His 6 tags at their N termini and were expressed from recombinant baculoviruses in Sf9 insect cells. glutathione S-transferase fusion proteins containing the N terminus (amino acids 1-312) and C terminus (amino acids 953-1269) of NDH II were as described previously (24).…”

Section: Methodsmentioning

confidence: 99%

Actinomycin D Induces Histone γ-H2AX Foci and Complex Formation of γ-H2AX with Ku70 and Nuclear DNA Helicase II

Mischo¹,

Hemmerich

Grosse³

et al. 2005

Journal of Biological Chemistry

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Formation of ␥-H2AX foci is a P. O.cellular response to genotoxic stress, such as DNA double strand breaks or stalled replication forks. Here we show that ␥-H2AX foci were also formed when cells were incubated with 0.5 g/ml DNA intercalating agent actinomycin D. In untreated cells, ␥-H2AX co-immunoprecipitated with Ku70, a subunit of DNA-dependent protein kinase, as well as with nuclear DNA helicase II (NDH II), a DEXH family helicase also known as RNA helicase A or DHX9. This association was increased manifold after actinomycin D treatment. DNA degradation diminished the amount of Ku70 associated with ␥-H2AX but not that of NDH II. In vitro binding studies with recombinant NDH II and H2AX phosphorylated by DNA-dependent protein kinase confirmed a direct physical interaction between NDH II and ␥-H2AX. Thereby, the NDH II DEXH domain alone, i.e. its catalytic core, was able to support binding to ␥-H2AX. Congruently, after actinomycin D treatment, NDH II accumulated in RNA-containing nuclear bodies that predominantly co-localized with ␥-H2AX foci. Taken together, these results suggest that histone ␥-H2AX promotes binding of NDH II to transcriptionally stalled sites on chromosomal DNA.The histone H2A family contains three members named H2A1-H2A2, H2AZ, and H2AX (for reviews, see Refs. 1 and 2). In mammals, 75-98% of H2A is represented by H2A1 and H2A2, whereas only 2-25% of all nucleosomes contain H2AX. Although the situation is different in yeast, where the two H2AX orthologs HTA1 and HTA2 account for 95% of the H2A complement, in both, H2AX plays an important role in DNA repair, particularly after inducing DNA double strand breaks (DSBs)

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“…Within the N-terminal region of RHA there are two copies of type A double-stranded RNA binding domains. Together with an RGG-box domain located at the C terminus, double-stranded RNA binding domains regulate RNA binding as well as helicase activities of RHA (4). RHA is a nuclear protein and shuttles between the nucleus and the cytoplasm with the assistance of a bidirectional nuclear transport domain consisting of 110 amino acids at the C terminus (5).…”

Section: Rna Helicase a (Rha)mentioning

confidence: 99%

Association of RNA Helicase A with Human Immunodeficiency Virus Type 1 Particles

Roy

Guo

et al. 2006

Journal of Biological Chemistry

132

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RNA helicase A (RHA) belongs to the DEAH family of proteins that are capable of unwinding double-stranded RNA structure. In addition to its involvement in the metabolism of cellular RNA, RHA has been shown to stimulate RNA transcription from the long terminal repeat promoter of human immunodeficiency virus type 1 (HIV-1) as well as to enhance Rev/Rev response element-mediated gene expression. In this study, we provide evidence that RHA associates with HIV-1 Gag in an RNA-dependent manner. This interaction results in specific incorporation of RHA into HIV-1 particles. Knockdown of endogenous RHA in virus producer cells leads to generation of HIV-1 particles that are less infectious in part as a result of restricted reverse transcription. Therefore, RHA represents the first example of cellular RNA helicases that participate in HIV-1 particle production and promote viral reverse transcription. RNA helicase A (RHA)2 is a member of the DEXH-box (where X can be any amino acid) family of proteins and is also termed DHX9 (1, 2). The DEXH-box proteins, together with the DEAD-box and the Ski2 family members, are referred to as RNA helicases that are able to rearrange the structures of RNA molecules (3). RHA contains a helicase core domain consisting of seven motifs that are conserved for all RNA helicases. Within the N-terminal region of RHA there are two copies of type A double-stranded RNA binding domains. Together with an RGG-box domain located at the C terminus, double-stranded RNA binding domains regulate RNA binding as well as helicase activities of RHA (4). RHA is a nuclear protein and shuttles between the nucleus and the cytoplasm with the assistance of a bidirectional nuclear transport domain consisting of 110 amino acids at the C terminus (5). This function of the RHA nuclear transport domain is subject to regulation of arginine methylation catalyzed by PRMT1 (protein-arginine methyltransferase 1) (6). RHA is able to unwind double-stranded RNA or DNA with the energy derived from hydrolysis of NTPs by virtue of its NTPase activity (1). This property enables RHA to participate in multiple cellular processes from RNA transcription to RNA processing to RNA nuclear export (7). These multiple functions underlie the vital role of RHA in the germ line proliferation and development of Caenorhabditis elegans (8) and also account for the early embryonic lethality observed with RHA knock-out mice (9).The regulation activity of RHA in RNA transcription is implicated by its presence within the RNA polymerase II holoenzyme complex. For example, RHA has been shown to bridge the interactions between RNA polymerase II and transcription co-activators such as CREB-binding protein and BRAC1 (breast cancer-specific tumor suppressor protein 1) (10, 11). RHA also directly interacts with the p65 subunit of NF-B and stimulates NF-B-mediated reporter gene expression (12). Involvement of RHA in transcription is further indicated by the function of its homologue in Drosophila, named the maleless (MLE) gene, that increases gene expression fr...

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Domain Structure of Human Nuclear DNA Helicase II (RNA Helicase A)

Cited by 110 publications

References 42 publications

BCL2 Translocation Defines a Unique Tumor Subset within the Germinal Center B-Cell-Like Diffuse Large B-Cell Lymphoma

BCL2 Translocation Defines a Unique Tumor Subset within the Germinal Center B-Cell-Like Diffuse Large B-Cell Lymphoma

Actinomycin D Induces Histone γ-H2AX Foci and Complex Formation of γ-H2AX with Ku70 and Nuclear DNA Helicase II

Association of RNA Helicase A with Human Immunodeficiency Virus Type 1 Particles

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