Evidence map›Paper›PMID 22973040›Full record

ArticleJournal of virology2012

The Vpx lentiviral accessory protein targets SAMHD1 for degradation in the nucleus.

Henning Hofmann, Eric C Logue, Nicolin Bloch, Waaqo Daddacha, Sylvie B Polsky, Megan L Schultz, Baek Kim, Nathaniel R Landau

Open access · bronzeAbstract read
In one paragraph

Article in Journal of virology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 96 papers.

0numbers the graph read from it
0cells of the map it votes in
96citing papers in PubMed
7.1field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

96 citing papers in PubMed, 129 citations in OpenAlex.

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  12. Advances in HIV Gene Therapy.International journal of molecular sciences · 2024
    Review
  13. Adaptation of SIVmac to baboon primary cells results in complete absence ofFrontiers in cellular and infection microbiology · 2024
    Article
  14. Review
  15. Article
  16. Article
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  20. Review

36 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 2 institutions in 1 country.

Henning HofmannMicrobiology Department, New York University School of Medicine, New York, New York, USA.
Eric C Logue
Nicolin Bloch
Waaqo Daddacha
Sylvie B Polsky
Megan L Schultz
Baek Kim
Nathaniel R Landau
New York University · USUniversity of Rochester Medical Center · US

Funding

Replication fidelity and lentiviral pathogenesisR01AI049781 · NIAID · UNIVERSITY OF ROCHESTER · PI KIM, BAEK · 2002 to 2016
$4.9M
SAMHD1 controls dNTP pool and HIV sensitivity to NRTIsR01GM104198 · NIGMS · UNIVERSITY OF ROCHESTER · PI KIM, BAEK · 2012 to 2018
$2.3M
Inverted two photon laser scanning microscope for host defenseS10RR023704 · NCRR · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI DUSTIN, MICHAEL LORAN · 2008 to 2008
$500k
Mechanistic Interplays between cPP Tract and RT Inhibitor Sensitivity of HIV-1F31GM095190 · NIGMS · UNIVERSITY OF ROCHESTER · PI DADDACHA, WAAQO BORU · 2011 to 2013
$109k
NCRR NIH HHS S10 RR023704NCRR NIH HHS S10 RR023704-01A1NIAID NIH HHS AI048781NIAID NIH HHS R01 AI049781NIGMS NIH HHS F31 GM095190NIGMS NIH HHS R01 GM104198PHS HHS A1067059
6 · The paper itself

Abstract

Sterile alpha motif domain- and HD domain-containing protein 1 (SAMHD1) is a deoxynucleoside triphosphohydrolase that restricts the replication of lentiviruses in myeloid cells by hydrolyzing the cellular deoxynucleotide triphosphates to a level below that which is required for reverse transcription. Human immunodeficiency virus type 2 (HIV-2) and some simian immunodeficiency viruses (SIVs) encode the accessory protein viral protein X (Vpx) that counteracts SAMHD1. Vpx recruits SAMHD1 to a cullin4A-RING E3 ubiquitin ligase (CRL4), which targets the enzyme for proteasomal degradation. Vpx and SAMHD1 both localize to the nucleus of the cell. We identified the nuclear localization sequence (NLS) of SAMHD1 as a conserved KRPR sequence at amino acid residues 11 to 14. SAMHD1 lacking a functional NLS localized to the cytoplasm but retained its triphosphohydrolase and antiviral activities. However, cytoplasmic SAMHD1 was resistant to Vpx-induced degradation, and its antiviral activity was not counteracted by Vpx. Cytoplasmic SAMHD1 interacted with Vpx and retained it in the cytoplasm. The inhibition of nuclear export with leptomycin B did not impair the ability of Vpx to degrade SAMHD1. These findings suggest that SAMHD1 is targeted by Vpx for ubiquitination and degradation in the nucleus.

Indexed as

ProteolysisAmino Acid SequenceCell NucleusCullin ProteinsHeLa CellsHumansImmunoblottingImmunoprecipitationMicroscopy, FluorescenceMonomeric GTP-Binding ProteinsNuclear Localization SignalsPlasmidsSAM Domain and HD Domain-Containing Protein 1UbiquitinationUbiquitin-Protein LigasesViral Regulatory and Accessory ProteinsCUL4A protein, humanCullin ProteinsMonomeric GTP-Binding ProteinsNuclear Localization SignalsSAM Domain and HD Domain-Containing Protein 1SAMHD1 protein, humanUbiquitin-Protein LigasesViral Regulatory and Accessory ProteinsVPX protein, Human immunodeficiency virus 2

Identifiers

PMID22973040
PMCPMC3497686
OpenAlexW2154750531

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.