Dynamic disruptions in nuclear envelope architecture and integrity induced by HIV-1 Vpr.
Human immunodeficiency virus-1 (HIV-1) Vpr expression halts the proliferation of human cells at or near the G2 cell-cycle checkpoint. The transition from G2 to mitosis is normally controlled by changes in the state of phosphorylation and subcellular compartmentalization of key cell-cycle regulatory proteins. In studies of the intracellular trafficking of these regulators, we unexpectedly found that wild-type Vpr, but not Vpr mutants impaired for G2 arrest, induced transient, localized herniations in the nuclear envelope (NE). These herniations were associated with defects in the nuclear lamina. Intermittently, these herniations ruptured, resulting in the mixing of nuclear and cytoplasmic components. These Vpr-induced NE changes probably contribute to the observed cell-cycle arrest.
de Noronha
C M
CM
Gladstone Institute of Virology and Immunology, Department of Medicine, University of California, San Francisco, CA 94103, USA.
Sherman
M P
MP
Lin
H W
HW
Cavrois
M V
MV
Moir
R D
RD
Goldman
R D
RD
Greene
W C
WC
D021581:Active Transport, Cell Nucleus; D018797:Cell Cycle Proteins / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism* / Q000821:virology; D019926:Cyclin B / Q000378:metabolism; D056744:Cyclin B1; D003593:Cytoplasm / Q000378:metabolism; D016195:G2 Phase; D016336:Gene Products, vpr / Q000235:genetics / Q000502:physiology*; D015497:HIV-1 / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D034921:Lamin Type B; D034882:Lamins; D008264:Macrophages / Q000821:virology; D008856:Microscopy, Fluorescence; D018715:Microscopy, Video; D008938:Mitosis; D009154:Mutation; D009685:Nuclear Envelope / Q000378:metabolism* / Q000648:ultrastructure; D028861:Nuclear Pore Complex Proteins / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D014162:Transfection; D016662:Virus Integration; D020687:cdc25 Phosphatases / Q000378:metabolism; D054325:vpr Gene Products, Human Immunodeficiency Virus
C534699:CCNB1 protein, human; D018797:Cell Cycle Proteins; D019926:Cyclin B; D056744:Cyclin B1; D016336:Gene Products, vpr; D034921:Lamin Type B; D034882:Lamins; D028861:Nuclear Pore Complex Proteins; D009687:Nuclear Proteins; D011993:Recombinant Fusion Proteins; D054325:vpr Gene Products, Human Immunodeficiency Virus; D011505:Protein-Tyrosine Kinases; C499349:WEE1 protein, human; C517009:CDC25C protein, human; D020687:cdc25 Phosphatases