14-3-3 theta binding to cell cycle regulatory factors is enhanced by HIV-1 Vpr

<p>Abstract</p> <p>Background</p> <p>Despite continuing advances in our understanding of AIDS pathogenesis, the mechanism of CD4+ T cell depletion in HIV-1-infected individuals remains unclear. The HIV-1 Vpr accessory protein causes cell death, likely through a mechanis...

Full description

Bibliographic Details
Main Authors: Sakai Keiko, Barnitz Robert A, Bolton Diane L, Lenardo Michael J
Format: Article
Language:English
Published: BMC 2008-04-01
Series:Biology Direct
Online Access:http://www.biology-direct.com/content/3/1/17
id doaj-530e4997b66e4a94b5fae1afb02ab21e
record_format Article
spelling doaj-530e4997b66e4a94b5fae1afb02ab21e2020-11-25T01:18:23ZengBMCBiology Direct1745-61502008-04-01311710.1186/1745-6150-3-1714-3-3 theta binding to cell cycle regulatory factors is enhanced by HIV-1 VprSakai KeikoBarnitz Robert ABolton Diane LLenardo Michael J<p>Abstract</p> <p>Background</p> <p>Despite continuing advances in our understanding of AIDS pathogenesis, the mechanism of CD4+ T cell depletion in HIV-1-infected individuals remains unclear. The HIV-1 Vpr accessory protein causes cell death, likely through a mechanism related to its ability to arrest cells in the G<sub>2</sub>,M phase. Recent evidence implicated the scaffold protein, 14-3-3, in Vpr cell cycle blockade.</p> <p>Results</p> <p>We found that in human T cells, 14-3-3 plays an active role in mediating Vpr-induced cell cycle arrest and reveal a dramatic increase in the amount of Cdk1, Cdc25C, and CyclinB1 bound to 14-3-3 θ during Vpr<sub>v</sub>-induced G<sub>2</sub>,M arrest. By contrast, a cell-cycle-arrest-dead Vpr mutant failed to augment 14-3-3 θ association with Cdk1 and CyclinB1. Moreover, G<sub>2</sub>,M arrest caused by HIV-1 infection strongly correlated with a disruption in 14-3-3 θ binding to centrosomal proteins, Plk1 and centrin. Finally, Vpr caused elevated levels of CyclinB1, Plk1, and Cdk1 in a complex with the nuclear transport and spindle assembly protein, importin β.</p> <p>Conclusion</p> <p>Thus, our data reveal a new facet of Vpr-induced cell cycle arrest involving previously unrecognized abnormal rearrangements of multiprotein assemblies containing key cell cycle regulatory proteins.</p> <p>Reviewers</p> <p>This article was reviewed by David Kaplan, Nathaniel R. Landau and Yan Zhou.</p> http://www.biology-direct.com/content/3/1/17
collection DOAJ
language English
format Article
sources DOAJ
author Sakai Keiko
Barnitz Robert A
Bolton Diane L
Lenardo Michael J
spellingShingle Sakai Keiko
Barnitz Robert A
Bolton Diane L
Lenardo Michael J
14-3-3 theta binding to cell cycle regulatory factors is enhanced by HIV-1 Vpr
Biology Direct
author_facet Sakai Keiko
Barnitz Robert A
Bolton Diane L
Lenardo Michael J
author_sort Sakai Keiko
title 14-3-3 theta binding to cell cycle regulatory factors is enhanced by HIV-1 Vpr
title_short 14-3-3 theta binding to cell cycle regulatory factors is enhanced by HIV-1 Vpr
title_full 14-3-3 theta binding to cell cycle regulatory factors is enhanced by HIV-1 Vpr
title_fullStr 14-3-3 theta binding to cell cycle regulatory factors is enhanced by HIV-1 Vpr
title_full_unstemmed 14-3-3 theta binding to cell cycle regulatory factors is enhanced by HIV-1 Vpr
title_sort 14-3-3 theta binding to cell cycle regulatory factors is enhanced by hiv-1 vpr
publisher BMC
series Biology Direct
issn 1745-6150
publishDate 2008-04-01
description <p>Abstract</p> <p>Background</p> <p>Despite continuing advances in our understanding of AIDS pathogenesis, the mechanism of CD4+ T cell depletion in HIV-1-infected individuals remains unclear. The HIV-1 Vpr accessory protein causes cell death, likely through a mechanism related to its ability to arrest cells in the G<sub>2</sub>,M phase. Recent evidence implicated the scaffold protein, 14-3-3, in Vpr cell cycle blockade.</p> <p>Results</p> <p>We found that in human T cells, 14-3-3 plays an active role in mediating Vpr-induced cell cycle arrest and reveal a dramatic increase in the amount of Cdk1, Cdc25C, and CyclinB1 bound to 14-3-3 θ during Vpr<sub>v</sub>-induced G<sub>2</sub>,M arrest. By contrast, a cell-cycle-arrest-dead Vpr mutant failed to augment 14-3-3 θ association with Cdk1 and CyclinB1. Moreover, G<sub>2</sub>,M arrest caused by HIV-1 infection strongly correlated with a disruption in 14-3-3 θ binding to centrosomal proteins, Plk1 and centrin. Finally, Vpr caused elevated levels of CyclinB1, Plk1, and Cdk1 in a complex with the nuclear transport and spindle assembly protein, importin β.</p> <p>Conclusion</p> <p>Thus, our data reveal a new facet of Vpr-induced cell cycle arrest involving previously unrecognized abnormal rearrangements of multiprotein assemblies containing key cell cycle regulatory proteins.</p> <p>Reviewers</p> <p>This article was reviewed by David Kaplan, Nathaniel R. Landau and Yan Zhou.</p>
url http://www.biology-direct.com/content/3/1/17
work_keys_str_mv AT sakaikeiko 1433thetabindingtocellcycleregulatoryfactorsisenhancedbyhiv1vpr
AT barnitzroberta 1433thetabindingtocellcycleregulatoryfactorsisenhancedbyhiv1vpr
AT boltondianel 1433thetabindingtocellcycleregulatoryfactorsisenhancedbyhiv1vpr
AT lenardomichaelj 1433thetabindingtocellcycleregulatoryfactorsisenhancedbyhiv1vpr
_version_ 1725142869165998080