Steroid-receptor fusion of the human immunodeficiency virus type 1 Rev transactivator: Mapping cryptic functions of the arginine-rich motif

Thomas J. Hope, Xiaojian Huang, David McDonald, Tristram G. Parslow*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

196 Scopus citations

Abstract

The human immunodeficiency virus type 1 (HIV-1) transactivator Rev is a nuclear protein that regulates expression of certain HIV-1 transcripts by binding to an RNA target element (the RRE) present in these transcripts. A short arginine-rich sequence in Rev contains the signals required to direct this protein into nuclei, where it associates preferentially with nucleoli. We created a steroid-inducible transactivator by fusing Rev with the steroid-binding domain of the glucocorticoid receptor (GR). This Rev/GR protein remains inactive in the cytoplasm when steroids are absent, but it enters the nucleus and initiates transactivation within minutes after exposure to dexamethasone. Although the GR moiety is sufficient to transport Rev/GR into nuclei, mutation of certain residues in the arginine-rich region blocks nucleolar localization and also inhibits transactivation. We find that other mutations in this region, however, can abolish the function of Rev/GR without affecting its localization; the latter phenotype may reflect a specific defect in binding of the RRE.

Original languageEnglish (US)
Pages (from-to)7787-7791
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume87
Issue number19
DOIs
StatePublished - 1990

Keywords

  • Acquired immunodeficiency syndrome
  • Glucocorticoid receptor

ASJC Scopus subject areas

  • General

Fingerprint Dive into the research topics of 'Steroid-receptor fusion of the human immunodeficiency virus type 1 Rev transactivator: Mapping cryptic functions of the arginine-rich motif'. Together they form a unique fingerprint.

Cite this