Does the human immunodeficiency virus Tat trans-activator contain a discrete activation domain?

Published

Journal Article

Human immunodeficiency virus type 1 (HIV-1) encodes a transcriptional trans-activator, termed Tat, that is absolutely required for viral replication in vitro. By analogy to other known transcription factors, it has been suggested that the HIV-1 Tat protein may contain discrete protein domains that determine sequence specificity and transcriptional activation potential. Here, we report the use of site-directed mutagenesis to examine the functional significance of two candidate activation domains within Tat. A 12 amino acid sequence adjacent to the N-terminus of the Tat protein, which includes a proposed acidic amphipathic alpha-helix activation motif, was found to contribute to, but be dispensable for, Tat function in vivo. In contrast, the integrity of a second potential Tat activation motif, centered on a lysine residue at position 41, was found to be essential for Tat function. However, Tat proteins mutated in this area displayed a fully recessive negative phenotype. Therefore, neither of these two regions of the Tat protein appear to be discrete activation domains. We conclude that previous attempts to categorize Tat as a modular transcription factor have not succeeded and suggest that the functional organization of this complex trans-activator remains to be defined.

Full Text

Duke Authors

Cited Authors

  • Tiley, LS; Brown, PH; Cullen, BR

Published Date

  • October 1990

Published In

Volume / Issue

  • 178 / 2

Start / End Page

  • 560 - 567

PubMed ID

  • 2219707

Pubmed Central ID

  • 2219707

Electronic International Standard Serial Number (EISSN)

  • 2514-4138

International Standard Serial Number (ISSN)

  • 1096-0341

Digital Object Identifier (DOI)

  • 10.1016/0042-6822(90)90354-t

Language

  • eng