Does the human immunodeficiency virus Tat trans-activator contain a discrete activation domain?
Journal Article (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
International Standard Serial Number (ISSN)
- 0042-6822
Digital Object Identifier (DOI)
- 10.1016/0042-6822(90)90354-t
Language
- eng
Conference Location
- United States