Important note: Information in this article was accurate in 1995. The state of the art may have changed since the publication date.
Mechanism of upregulation of IL-4 receptors by human immunodeficiency virus (HIV-1) tat gene (Meeting abstract).
Proc Annu Meet Am Assoc Cancer Res; 36:A241 1995. Unique Identifier : AIDSLINE ICDB/95608021 Husain SR; Leland P; Puri RK; Laboratory of Molecular Tumor Biology, Division of Cell and Gene; Therapies, Center for Biologics Evaluation and Research, FDA,; Bethesda, MD 20892
Abstract:
The human immunodeficiency virus type 1 (HIV-1) regulatory gene, tat, encodes an early trans-activator protein (Tat) necessary for virus replication. We have recently reported that HIV-1 tat gene upregulated both protein and mRNA levels of interleukin 4 receptors (IL-4R) on a human B-lymphoblastoid cell line (Raji). In the present study, we show that in Raji cells, 125I-IL-4 crosslinked to two major proteins at 140 kD and 70 kD. Although, the level of both proteins increased in tat transfected cells. The binding characteristics of IL-4R on control and tat transfected Raji cells were similar. To understand the mechanism of upregulation of IL-4R by tat gene, the stability of both the proteins and mRNA as well as the level of IL-4R gene transcription were examined in Raji and Raji-tat cells. By actinomycin D chase experiment, we observed that the half-life of IL-4R protein (t1/2 3.5 hr) and mRNA transcripts (t1/2 2.5 hr) were similar in both control and tat transfected cells. In contrast, nuclear run-on assays showed that the rate of IL-4R mRNA transcription significantly increased in Raji-tat compared to Raji cells. These data indicate that HIV-1 tat gene up-regulates IL-4R expression by increasing the transcription rate rather than posttranscriptional mRNA stabilization of either the mRNA or the protein.
Keywords: Cell Line Dactinomycin *Genes, tat Human Receptors, Mitogen/*GENETICS RNA Processing, Post-Transcriptional RNA, Messenger/GENETICS Transcription, Genetic *Up-Regulation (Physiology) ABSTRACT 950630
M9561164
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