Linked Life Data

21521785

Source:http://linkedlifedata.com/resource/pubmed/id/21521785

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
24
pubmed:dateCreated
2011-6-17
pubmed:abstractText
HIV-1 viral protein U (Vpu) is involved in ubiquitination and degradation of BM stromal cell Ag 2 and surface receptor CD4 through their recruitment to SCF(?-TrcP) (Skp1/Cul1/F-box) ubiquitin ligase (SCF) complex. Here, we show that specific interaction of wild-type Vpu protein with SCF complex leads to inhibition of ubiquitination and proteasomal degradation of p53 protein in a ?-TrcP-dependent manner. Successful interaction of SCF(?-TrcP) complex with ?-TrcP binding motif (DS(52)GNES(56)) present in Vpu is essential because mutant Vpu possessing specific alanine substitutions (DA(52)GNEA(56)) in the ?-TrcP binding motif not only failed to stabilize p53 protein but was also unable to inhibit ubiquitination of p53 protein. Furthermore, Vpu competes efficiently with the interaction of p53 protein with the ?-TrcP subunit of the SCF complex and inhibits subsequent ubiquitination of p53 proteins in a dose-dependent manner. We also observed potent apoptotic activity in a p53 null cell line (H-1299) that was cotransfected with p53 and Vpu-expressing plasmids. Furthermore, MOLT-3 (human T-lymphoblast) cells when infected with vesicular stomatitis virus glycoprotein-pseudotypic HIV-1 possessing wild-type vpu gene exhibited maximum activation of p53/Bax proteins and p53-mediated cell death. These findings establish a novel function of Vpu in modulating the stability of p53 protein that correlates positively with apoptosis during late stages of HIV-1 infection.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
1528-0020
pubmed:author
pubmed:issnType
Electronic
pubmed:day
16
pubmed:volume
117
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
6600-7
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
Inhibition of ?-TrcP-dependent ubiquitination of p53 by HIV-1 Vpu promotes p53-mediated apoptosis in human T cells.
pubmed:affiliation
Laboratory of Virology, National Institute of Immunology, New Delhi, India.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't