Pergamon Life Sciences, Vol. 54, No. 18, pp. PL 313-314, 1994 Copyright © 1994 Elsevier Science Ltd Printed in the USA. All rights reserved 0024-3205/94 $6.00 + .00 PHARMACOLOGY LETTERS Letter to the Editor HIV-TAR HOMOLOGY WITH HUMAN c-FES ONCOGENE To the Editor: HIV mRNA contains a stable RNA stem-loop structure, TAR, on the 5 ' end of the message (1). This region has been shown to specifically bind to the HIV regulatory protein, tat (transactivator). Tat induces its effects on HIV transactivation via interaction with a cis- acting site in CUGGG pentanucleotide in the loop context of the RNA stem-loop structure (2). The mechanism of the tat-induced transactivation of the HIV-provirus has been recently demonstrated to involve interaction of the tat-TAR with tat-binding proteins involving both post-translational and transcriptional events (3). Several investigators have shown that soluble tat protein can inhibit normal T cell proliferative responses (4-6). Since TAR is absent in normal cells, TAR-independent mechanisms of tat-mediated actions may be involved. One of the hypotheses of the mechanism of the tat-mediated inhibitory effects in normal T cells is by a possible interaction of tat with a TAR-like RNA sequence. Table 1 shows the RNA sequence of TAR that has been shown to be important for interaction with tat (7). The sequence of the deduced complementary DNA strand was compared with known nucleotide sequences in the GeneBank database. As shown below, the nucleotide sequence of the c-fes oncogene was found to be homologous to the TAR-loop cDNA sequence. Table 1. Nucleotide Sequence Comparisons: TAR RNA sequence (ref 7) 5 ' deduced cDNA sequence homologous c-fes sequence 3' (acc# x06292, ref 8) 1292 CCU GGG AGC UCU CUG G 3 ' GGA CCC TCG AGA GAC C GGA CCC cCG gGA GAC C 5 ' 1297 Thus, 14 out of 16 residues in the TAR-loop sequence are homologous to the human c-fes proto-oncogene nucleotide sequence. The p92 fes oncogene product is a protein-tyrosine kinase, implicated in the signaling pathway triggered by GM-GSF and IL-3 (9). It is possible that tat interacts with c-fes mRNA or the c-fes gene itself and interferes with the signal transduction cascade in normal T cells. References 1. B.R. CULLEN, Cell 63 655-657 (1990). 2. S. FENG and E.C. HOLLAND, Nature 334 165-167 (1985). 3. K.A. JONES, Curr. Op. Cell Biol. 5 461-468 (1993). 4. R. VISCIDI, K. MAYUR, H.M. LEDERMAN and A.D. FRANKEL, Science 246 1606-1608 (1989).