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HMBA releases P-TEFb from HEXIM1 and 7SK snRNA via PI3K/Akt and activities HIV transcription
ID
Contreras, Xavier
(
Author
),
ID
Barborič, Matjaž
(
Author
),
ID
Lenasi, Tina
(
Author
),
ID
Peterlin, Matija Boris
(
Author
)
URL - Presentation file, Visit
http://pathogens.plosjournals.org/perlserv/?request=get-document&doi=10.1371%2Fjournal.ppat.0030146
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Abstract
Hexamethylene bisacetamide (HMBA) is a potent inducer of cell differentiation and HIV production in chronically infected cells. However, its mechanism of action remains poorly defined. In this study, we demonstrate that HMBA activates transiently the PI3K/Act pathway, which leads to the phosphorylation of HEXIM1 and the subsequent release of active positive transcription elongation factor b (P-TEFb) from its transcriptionally inactivecomplex with HEXIM1 and 7SK small nuclear RNA (snRNA). As a result, P-TEFb is recruited tothe HIV promotoer to stimulate transcription elongation and viral production. Despite the continuous presence of HMBA, the released P-TEFb reassembles rapidly with 7SK sn RNA and HEXIM1. In contrast, a mutant HEXIM1 protein that cannot be phosphorrylated and released from P-TEFb and 7SK snRNA via the PI3K/Act pathway antagonizes this HMBA-mediated induction of viral production. Thus, our studies reveal how transcription is induced by HMBA and suggest how modifications in the equilibrium between active and inactive P-TEFb could contribute to cell differentiation.
Language:
English
Keywords:
infekcijske bolezni
,
AIDS
,
HIV
,
molekularna genetika
Work type:
Not categorized
Typology:
1.01 - Original Scientific Article
Organization:
BF - Biotechnical Faculty
Year:
2007
Number of pages:
Str. 1459-1469
Numbering:
Letn. 3, št. 10
PID:
20.500.12556/RUL-36490
UDC:
575
ISSN on article:
1553-7366
COBISS.SI-ID:
2204808
Publication date in RUL:
10.07.2015
Views:
2308
Downloads:
254
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Record is a part of a journal
Title:
PLOS pathogens
Publisher:
Public Library of Science
ISSN:
1553-7366
COBISS.SI-ID:
513029401
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