HMBA releases P-TEFb from HEXIM1 and 7SK snRNA via PI3K/Akt and activities HIV transcription
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.
2007
2015-07-10 12:29:36
1033
infekcijske bolezni, AIDS, HIV, molekularna genetika,
r6
Xavier
Contreras
70
Matjaž
Barborič
70
Tina
Lenasi
70
Matija Boris
Peterlin
70
UDK
4
575
ISSN pri članku
9
1553-7366
COBISS_ID
3
2204808
OceCobissID
13
513029401
0
Predstavitvena datoteka
2015-07-10 12:29:36