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

Koh Fujinaga; Dan Irwin; Yehong Huang; Ran Taube; Takeshi Kurosu; B Matija Peterlin

doi:10.1128/MCB.24.2.787-795.2004

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

Mol Cell Biol. 2004 Jan;24(2):787-95. doi: 10.1128/MCB.24.2.787-795.2004.

Authors

Koh Fujinaga¹, Dan Irwin, Yehong Huang, Ran Taube, Takeshi Kurosu, B Matija Peterlin

Affiliation

¹ Department of Medicine, Rosalind Russell Medical Research Center, University of California at San Francisco, 3rd and Parnassus Avenue, San Francisco, CA 94143-0703, USA. kxf32@cwru.edu

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.

Publication types

Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

MeSH terms

Cell Line
Chromosomal Proteins, Non-Histone / genetics
Chromosomal Proteins, Non-Histone / metabolism
Gene Products, tat / genetics
Gene Products, tat / metabolism
HIV Long Terminal Repeat*
HIV-1 / genetics*
HIV-1 / metabolism*
HIV-1 / physiology
Humans
Models, Biological
Nuclear Proteins / genetics
Nuclear Proteins / metabolism*
Phosphorylation
Positive Transcriptional Elongation Factor B / genetics
Positive Transcriptional Elongation Factor B / metabolism*
Protein Binding
Recombinant Fusion Proteins / genetics
Recombinant Fusion Proteins / metabolism
Transcription Factors / genetics
Transcription Factors / metabolism
Transcription, Genetic
Transcriptional Elongation Factors / genetics
Transcriptional Elongation Factors / metabolism
Virus Replication
tat Gene Products, Human Immunodeficiency Virus

Substances

Chromosomal Proteins, Non-Histone
Gene Products, tat
Nuclear Proteins
Recombinant Fusion Proteins
Transcription Factors
Transcriptional Elongation Factors
negative elongation factor
tat Gene Products, Human Immunodeficiency Virus
SPT5 transcriptional elongation factor
Positive Transcriptional Elongation Factor B