Dynamics of human immunodeficiency virus transcription: P-TEFb phosphorylates RD and dissociates negative effectors from the transactivation response element.

Abstract:

:The elongation of transcription is a highly regulated process that requires negative and positive effectors. By binding the double-stranded stem in the transactivation response (TAR) element, RD protein from the negative transcription elongation factor (NELF) inhibits basal transcription from the long terminal repeat of the human immunodeficiency virus type 1 (HIVLTR). Tat and its cellular cofactor, the positive transcription elongation factor b (P-TEFb), overcome this negative effect. Cdk9 in P-TEFb also phosphorylates RD at sites next to its RNA recognition motif. A mutant RD protein that mimics its phosphorylated form no longer binds TAR nor represses HIV transcription. In sharp contrast, a mutant RD protein that cannot be phosphorylated by P-TEFb functions as a dominant-negative effector and inhibits Tat transactivation. These results better define the transition from abortive to productive transcription and thus replication of HIV.

journal_name

Mol Cell Biol

authors

Fujinaga K,Irwin D,Huang Y,Taube R,Kurosu T,Peterlin BM

doi

10.1128/mcb.24.2.787-795.2004

subject

Has Abstract

pub_date

2004-01-01 00:00:00

pages

787-95

issue

2

eissn

0270-7306

issn

1098-5549

journal_volume

24

pub_type

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