1-40 1 AN 94365994 AU Perkins ND. Agranoff AB. Duckett CS. Nabel GJ.

IN Howard Hughes Medical Institute, Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor 48109-0650. TI Transcription factor AP-2 regulates human immunodeficiency virus type 1 gene expression. SO Journal of Virology. 68(10):6820-3, 1994. JC kcv SB C, L AB Human immunodeficiency virus type 1 (HIV-1) gene expression is regulated by an enhancer region composed of multiple potential cis-acting regulatory sites. Here, we describe binding sites for the transcription factor AP-2 in the HIV-1 long terminal repeat which modulate HIV enhancer function. One site is embedded within the two previously described kappa B elements, and a second site is detected further downstream. DNase I footprinting and electrophoretic mobility shift assay experiments demonstrated that AP-2 binds to the site between the kappa B elements. Interestingly, AP-2 and NF-kappa B bind to this region in a mutually exclusive manner. Mutations which disrupt this AP-2-binding site lower basal levels of transcription but do not affect NF-kappa B-mediated induction by tumor necrosis factor alpha in Jurkat T leukemia cells. DE Base Sequence. Binding Sites. Binding, Competitive. Cell Line. Consensus Sequence. DNA, Viral/ge [Genetics]. DNA, Viral/me [Metabolism]. *DNA-Binding Proteins/me [Metabolism]. *Enhancer Elements (Genetics). *Gene Expression Regulation, Viral. *HIV-1/ge [Genetics]. *HIV-1/me [Metabolism]. Human. Molecular Sequence Data. Promoter Regions (Genetics). Recombinant Proteins/me [Metabolism]. Regulatory Sequences, Nucleic Acid. Support, Non-U.S. Gov't. Support, U.S. Gov't, P.H.S.. TATA Box. *Transcription Factors/me [Metabolism]. RN 0 (enhancer-binding protein AP-2). 0 (DNA-Binding Proteins). 0 (DNA, Viral). 0 (Recombinant Proteins). 0 (Transcription Factors). IS 0022-538X PT Journal Article. LG English UP 9411 9 94697554 Taipale J. Matikainen S. Hurme M. Keski-Oja J. Dept. of Virology, Univ. of Helsinki, SF-00290 Helsinki 29, Finland Control of TGF-beta 1, its latent form binding protein (LTBP) and type II receptor expression during differentiation of human myeloid leukemia cell lines (Meeting abstract). SO EACR-12: 12th Biennial Meeting of the European Association for Cancer Research. April 4-7, 1993, Brussels, Belgium AB The human myeloid leukemia cell lines HL-60 and THP-1 were used to study the role of TGF-beta in hematopoietic cell growth control and differentiation. HT-1080 fibrosarcoma cell line, which produces relatively high amounts of latent TGF-beta 1 and expresses type II TGF-beta receptors was used as a control. Northern hybridization analyses indicated that the basal levels of latent TGF-beta binding protein and type II TGF-beta receptor mRNAs were extremely low in untreated THP-1 and HL-60 cells compared to HT-1080. TGF-beta 1 mRNA was expressed at comparable levels in HT-1080 and THP-1 cells, while in HL-60 cells the levels were undetectable. Differentiation of the myeloid leukemia cell lines was induced by the phorbol ester PMA or by retinoic acid. The MRNA levels of TGF-beta 1, LTBP and type II TGF-beta receptor were induced by PMA and tumor necrosis factor-alpha in HL-60 and THP-1 cells, with max induction occurring after AN AU IN TI

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24-hr stimulation as shown by Northern hybridization. Retinoic acid induced these mRNAs only in HL-60 cells, and the effect was much slower, requiring 3-day stimulation. No effects by these stimulators were seen in HT-1080 cells within 24 hr suggesting that the changes in gene expression are related to the differentiation of THP-1 and HL-60 cells. The results indicate that multiple TGF-beta-related genes are coordinately upregulated during myeloid differentiation. The low basal expression level of type II TGF-beta receptor in undifferentiated cells could contribute to the escape of malignant cells from normal growth control mechanisms. *Cell Differentiation/de [Drug Effects]. Human. *Leukemia, Myeloid/pa [Pathology]. Leukemia, Myeloid/th [Therapy]. RNA, Messenger/me [Metabolism]. Receptors, Transforming Growth Factor beta/me [Metabolism]. Tetradecanoylphorbol Acetate/pd [Pharmacology]. Transforming Growth Factor beta/ge [Genetics]. *Transforming Growth Factor beta/pd [Pharmacology]. Tretinoin/pd [Pharmacology]. Tumor Cells, Cultured. 0 (RNA, Messenger). 0 (Receptors, Transforming Growth Factor beta). 16561-29-8 (Tetradecanoylphorbol Acetate). 0 (Transforming Growth Factor beta). 302-79-4 (Tretinoin). Meeting Abstract. English 9411