scholarly journals Human T-cell lymphotropic virus type 1 infection of CD34+hematopoietic progenitor cells induces cell cycle arrest by modulation of p21cip1/waf1and survivin

Stem Cells ◽  
2013 ◽  
Vol 31 (9) ◽  
pp. 2031-2031
Author(s):  
Prabal Banerjee ◽  
Michelle Sieburg ◽  
Elizabeth Samuelson ◽  
Gerold Feuer
Keyword(s):  
Cell Cycle ◽  
T Cell ◽  
Cell Cycle Arrest ◽  
Progenitor Cells ◽  
Virus Type ◽  
Hematopoietic Progenitor Cells ◽  
Hematopoietic Progenitor ◽  
Cycle Arrest ◽  
Human T Cell

scholarly journals Induction of Cell Cycle Arrest by Human T-Cell Lymphotropic Virus Type 1 Tax in Hematopoietic Progenitor (CD34+) Cells: Modulation of p21cip1/waf1 and p27kip1 Expression

2005 ◽  
Vol 79 (22) ◽  
pp. 14069-14078 ◽  
Author(s):  
Adam Tripp ◽  
Prabal Banerjee ◽  
Michelle Sieburg ◽  
Vicente Planelles ◽  
Fengzhi Li ◽  
...  
Keyword(s):  
Cell Cycle ◽  
T Cell ◽  
Cell Cycle Arrest ◽  
Progenitor Cells ◽  
Virus Type ◽  
Hematopoietic Progenitor Cells ◽  
Hematopoietic Progenitor ◽  
Cycle Arrest ◽  
Human T Cell

ABSTRACT Human T-cell lymphotropic virus type 1 (HTLV-1) is the etiologic agent of adult T-cell leukemia, an aggressive CD4+ malignancy. Although HTLV-2 is highly homologous to HTLV-1, infection with HTLV-2 has not been associated with lymphoproliferative disorders. Lentivirus-mediated transduction of CD34+ cells with HTLV-1 Tax (Tax1) induced G0/G1 cell cycle arrest and resulted in the concomitant suppression of multilineage hematopoiesis in vitro. Tax1 induced transcriptional upregulation of the cdk inhibitors p21cip1/waf1 (p21) and p27kip1 (p27), and marked suppression of hematopoiesis in immature (CD34+/CD38−) hematopoietic progenitor cells in comparison to CD34+/CD38+ cells. HTLV-1 infection of CD34+ cells also induced p21 and p27 expression. Tax1 also protected CD34+ cells from serum withdrawal-mediated apoptosis. In contrast, HTLV-2 Tax (Tax2) did not detectably alter p21 or p27 gene expression, failed to induce cell cycle arrest, failed to suppress hematopoiesis in CD34+ cells, and did not protect cells from programmed cell death. A Tax2/Tax1 chimera encoding the C-terminal 53 amino acids of Tax1 fused to Tax2 (Tax221) displayed a phenotype in CD34+ cells similar to that of Tax1, suggesting that unique domains encoded within the C terminus of Tax1 may account for the phenotypes displayed in human hematopoietic progenitor cells. These remarkable differences in the activities of Tax1 and Tax2 in CD34+ hematopoietic progenitor cells may underlie the sharp differences observed in the pathogenesis resulting from infection with HTLV-1 and HTLV-2.

scholarly journals Human T-cell leukemia virus type 1 Tax releases cell cycle arrest induced by p16INK4a.

1997 ◽  
Vol 71 (3) ◽  
pp. 1956-1962 ◽  
Author(s):  
K G Low ◽  
L F Dorner ◽  
D B Fernando ◽  
J Grossman ◽  
K T Jeang ◽  
...  
Keyword(s):  
Cell Cycle ◽  
T Cell ◽  
Cell Cycle Arrest ◽  
Leukemia Virus ◽  
Cell Leukemia ◽  
Cell Leukemia Virus Type ◽  
Cycle Arrest ◽  
Human T Cell ◽  
T Cell Leukemia Virus

scholarly journals H4 Histamine Receptors Mediate Cell Cycle Arrest in Growth Factor-Induced Murine and Human Hematopoietic Progenitor Cells

PLoS ONE ◽  
2009 ◽  
Vol 4 (8) ◽  
pp. e6504 ◽  
Author(s):  
Anne-France Petit-Bertron ◽  
François Machavoine ◽  
Marie Paule Defresne ◽  
Michel Gillard ◽  
Pierre Chatelain ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Growth Factor ◽  
Cell Cycle Arrest ◽  
Progenitor Cells ◽  
Histamine Receptors ◽  
Hematopoietic Progenitor Cells ◽  
Hematopoietic Progenitor ◽  
Cycle Arrest ◽  
Mediate Cell

scholarly journals Human Immunodeficiency Virus Type 1 (HIV-1) Vpr Enhances Expression from Unintegrated HIV-1 DNA

2003 ◽  
Vol 77 (7) ◽  
pp. 3962-3972 ◽  
Author(s):  
Betty Poon ◽  
Irvin S. Y. Chen
Keyword(s):  
Cell Cycle ◽  
Human Immunodeficiency Virus ◽  
Cell Cycle Arrest ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Viral Dna ◽  
Cycle Arrest ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT Retroviral DNA synthesized prior to integration, termed unintegrated viral DNA, is classically believed to be transcriptionally inert and to serve only as a precursor to the transcriptionally active integrated proviral DNA form. However, it has recently been found to be expressed under some circumstances during human immunodeficiency virus type 1 (HIV-1) replication and may play a significant role in HIV-1 pathogenesis. HIV-1 Vpr is a virion-associated accessory protein that is critical for HIV-1 replication in nondividing cells and induces cell cycle arrest and apoptosis. We find that Vpr, either expressed de novo or released from virions following viral entry, is essential for unintegrated viral DNA expression. HIV-1 mutants defective for integration in either the integrase catalytic domain or the cis-acting att sites can express unintegrated viral DNA at levels similar to that of wild-type HIV-1, but only in the presence of Vpr. In the absence of Vpr, the expression of unintegrated viral DNA decreases 10- to 20-fold. Vpr does not affect the efficiency of integration from integrase-defective HIV-1. Vpr-mediated enhancement of expression from integrase-defective HIV-1 requires that the viral DNA be generated in cells through infection and is mediated via a template that declines over time. Vpr activation of expression does not require exclusive nuclear localization of Vpr nor does it correlate with Vpr-mediated cell cycle arrest. These results attribute a new function to HIV-1 Vpr and implicate Vpr as a critical component in expression from unintegrated HIV-1 DNA.

scholarly journals Human Immunodeficiency Virus Type 1 Vpr Induces G2 Checkpoint Activation by Interacting with the Splicing Factor SAP145

2006 ◽  
Vol 26 (21) ◽  
pp. 8149-8158 ◽  
Author(s):  
Yasuhiko Terada ◽  
Yuko Yasuda
Keyword(s):  
Cell Cycle ◽  
Human Immunodeficiency Virus ◽  
Cell Cycle Arrest ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Splicing Factor ◽  
Checkpoint Activation ◽  
Cycle Arrest ◽  
Immunodeficiency Virus

ABSTRACT Vpr, the viral protein R of human immunodeficiency virus type 1, induces G2 cell cycle arrest and apoptosis in mammalian cells via ATR (for “ataxia-telangiectasia-mediated and Rad3-related”) checkpoint activation. The expression of Vpr induces the formation of the γ-histone 2A variant X (H2AX) and breast cancer susceptibility protein 1 (BRCA1) nuclear foci, and a C-terminal domain is required for Vpr-induced ATR activation and its nuclear localization. However, the cellular target of Vpr, as well as the mechanism of G2 checkpoint activation, was unknown. Here we report that Vpr induces checkpoint activation and G2 arrest by binding to the CUS1 domain of SAP145 and interfering with the functions of the SAP145 and SAP49 proteins, two subunits of the multimeric splicing factor 3b (SF3b). Vpr interacts with and colocalizes with SAP145 through its C-terminal domain in a speckled distribution. The depletion of either SAP145 or SAP49 leads to checkpoint-mediated G2 cell cycle arrest through the induction of nuclear foci containing γ-H2AX and BRCA1. In addition, the expression of Vpr excludes SAP49 from the nuclear speckles and inhibits the formation of the SAP145-SAP49 complex. To conclude, these results point out the unexpected roles of the SAP145-SAP49 splicing factors in cell cycle progression and suggest that cellular expression of Vpr induces checkpoint activation and G2 arrest by interfering with the function of SAP145-SAP49 complex in host cells.

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