HMBA releases P-TEFb from HEXIM1 and 7SK snRNA via PI3K/Akt and activities HIV transcription

Contreras, Xavier (author), Barborič, Matjaž (author), Lenasi, Tina (author), Peterlin, Matija Boris (author)

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

Record is a part of a journal

• Title: PLOS pathogens
• Publisher: Public Library of Science
• ISSN: 1553-7366
• COBISS.SI-ID: 513029401