Biomedical subjects

H Kung

Publications and source records attributed to H Kung.

At least 19 recordsLinked to original sources

PubMed2001

The fluorescent Congo red derivative, (trans, trans)-1-bromo-2,5-bis-(3-hydroxycarbonyl-4-hydroxy)styrylbenzene (BSB), labels diverse beta-pleated sheet structures in postmortem human neurodegenerative disease brains.

A novel Congo red-derived fluorescent probe (trans, trans),-1-bromo-2,5-bis-(3-hydroxycarbonyl-4-hydroxy)styrylbenzene (BSB) that binds to amyloid plaques of postmortem Alzheimer's disease brains and in transgenic mouse brains in vivo was designed as a prototype imaging agent for Alzheimer's disease. In the current study, we used BSB to probe postmortem tissues from patients with various neurodegenerative diseases with diagnostic lesions characterized by fibrillar intra- or extracellular lesions and compared these results with standard histochemical dyes such as thioflavin S and immunohistochemical stains specific for the same lesions. These data show that BSB binds not only to extracellular amyloid beta protein, but also many intracellular lesions composed of abnormal tau and synuclein proteins and suggests that radioiodinated BSB derivatives or related ligands may be useful imaging agents to monitor diverse amyloids in vivo.

Adult↗

PubMed2000

Stepwise genetic changes associated with progression of nontumorigenic HPV-18 immortalized human prostate cancer-derived cell line to a malignant phenotype.

Cytogenetics, fluorescence in situ hybridization (FISH), and comparative genomic hybridization (CGH) were used to identify genes that are involved in the development and progression of prostate cancer. For that purpose, we chose a cell line established in vitro from a prostatic adenocarcinoma which was nontumorigenic in nude mice and followed its progression to a tumorigenic cell line. Stepwise changes were observed in the cell line as it became tumorigenic. The composite karyotype at the nontumorigenic stage (CA-HPV-10) was 68 approximately 77,XXY,-(1, 9, 13, 14, 19, 22),+(4, 5, 11, 18, 20, 21),+(del(1) (q23q31)=M1 (two copies), +der(9)t(1;9)(q24 approximately q31;p23)=M5(two copies), der(14)t(14;?)(q10;?)=M17 in the majority of metaphases. These two derivative chromosomes were also observed a previous study. Our CGH analysis clearly showed that this deleted region in M1 is, in fact, translocated with derivative M5 and, in reality, is amplified. The cell line established from nodule (SCID 5019 p11), showed a number of new changes, as described; however, the most significant change was amplification of the 8q23 approximately qter region, harboring c-myc. This region was translocated with chromosomes 2, 4, and 16 as der(2)t(2;8)(q33;q23)=M12, der(4)t(4;8)(q34;q23)=M11, and der(16)t(8;16)(q24;q21)=M9. We deduce from our study that amplification of c-myc and other genes in the 8q23 approximately qter region were important in progression but did not lead to tumorigenicity. The population that became tumorigenic (SCID 5019 II) showed almost all of the same changes in the karyotype as observed in the nodular cell line; the only significant change was the appearance of der(11)t(4;11)(q32;q22)=M7 and the addition of another copy of t(3q;7p)=M2. These new changes lead to loss of chromosomes 3p, 4pter approximately q34, 6, 7q21 approximately qter, 11q22 approximately qter, and 18q, and gain of 3q, 7p, 8q23 approximately qter, and 11pter approximately q22, before the cell line became tumorigenic. The clonal selection of the population is proven by the presence of a number of the same derivative chromosomes in both the nodular and tumorigenic cell line. As it progressed to tumorigenicity, some of the same changes observed in the original study re-appear at different stages of malignancy, although it was absent in the nontumorigenic cell line. These are: der(16)t(8;16)(q24;q21)=M9 in the nodular cell line and der(11)t(4;11)(q32;q22)=M7 in the tumorigenic cell line. In our system, amplification of c-myc and other genes in der(2)t(2;8)(q33;q23)=M12,der(4) t(4;8)(q34;q23)=M11 together with the presence of der(16)t(8;16)(q24;q21)=M9 and der(11)t(4;11)(q32;q22)=M5 makes the cell line tumorigenic. It is either nontumorigenic, with the presence of a marker equivalent to der(16)=M9 and der(11)=M7 observed in the original study, and only nodular (SCID 5019 p11, present study), with the presence of number of markers with c-myc amplification (M9, M11, and M12). There is accumulation of all the above-mentioned changes in the same cell before it becomes tumorigenic.

Aneuploidy↗

PubMed2000

A novel putative transcription factor protein MYT2 that preferentially binds supercoiled DNA and induces DNA synthesis in quiescent cells.

Myelin transcription factor 2 (MYT2), a putative transcription factor found in the human central nervous system, was cloned from an expression cDNA library from human T-cells. MYT2 shares weak similarity to bacterial type I topoisomerases and shares 63% sequence identity to a replicase from Leuconostoc mesenteroides. MYT2 preferentially binds supercoiled DNA (scDNA). Incubation of MYT2 and scDNA at or above equal molar ratios generated topoisomer-like patterns that were abolished by deproteination. Thus, MYT2 appears to relax scDNA via a non-enzymatic mechanism. The banding pattern of MYT2-scDNA complexes was shown to be quantisized, saturable and sequence-independent. Microinjection of MYT2 mRNA induced G(o) growth-arrested NIH 3T3 cells to enter the S phase of the cell cycle.

3T3 Cells↗

PubMed2000

Mouse peroxiredoxin V is a thioredoxin peroxidase that inhibits p53-induced apoptosis.

We have identified human and mouse peroxiredoxin V (Prx-V) by virtue of the sequence homologies to yeast peroxisomal antioxidant enzyme PMP20. Prx-V represents the fifth of the six currently known subfamilies of mammalian peroxiredoxins. It is a novel organellar enzyme that has orthologs in bacteria. Biochemically, Prx-V is a thioredoxin peroxidase. One important aspect of p53 function in mammalian cells involves induction of apoptosis likely mediated by redox. We show that overexpression of Prx-V prevented the p53-dependent generation of reactive oxygen species. Likewise, Prx-V inhibited p53-induced apoptosis. Thus, Prx-V is critically involved in intracellular redox signaling.

Amino Acid Sequence↗

PubMed2000

Hepatitis C virus core protein-induced loss of LZIP function correlates with cellular transformation.

Hepatitis C virus (HCV) is the major etiological agent of blood-borne non-A non-B hepatitis and a leading cause of liver cirrhosis and hepatocellular carcinoma worldwide. HCV core protein is a multifunctional protein with regulatory functions in cellular transcription and virus-induced transformation and pathogenesis. Here we report on the identification of a bZIP nuclear transcription protein as an HCV core cofactor for transformation. This bZIP factor, designated LZIP, activates CRE-dependent transcription and regulates cell proliferation. Loss of LZIP function in NIH 3T3 cells triggers morphological transformation and anchorage-independent growth. We show that HCV core protein aberrantly sequesters LZIP in the cytoplasm, inactivates LZIP function and potentiates cellular transformation. Our findings suggest that LZIP might serve a novel cellular tumor suppressor function that is targeted by the HCV core.

3T3 Cells↗

PubMed2000

The flavonoid baicalin exhibits anti-inflammatory activity by binding to chemokines.

Baicalin (BA) is a flavonoid compound purified from the medicinal plant Scutellaria baicalensis Georgi and has been reported to possess anti-inflammatory and anti-viral activities. In order to elucidate the mechanism(s) of action of BA, we tested whether BA could interfere with chemokines or chemokine receptors, which are critical mediators of inflammation and infection. We observed that BA inhibited the binding of a number of chemokines to human leukocytes or cells transfected to express specific chemokine receptors. This was associated with a reduced capacity of the chemokines to induce cell migration. Co-injection of BA with CXC chemokine interleukin-8 (IL-8) into rat skin significantly inhibited IL-8 elicited neutrophil infiltration. BA did not directly compete with chemokines for binding to receptors, but rather acted through its selective binding to chemokine ligands. This conclusion was supported by the fact that BA cross-linked to oxime resin bound chemokines of the CXC (stromal cell-derived factor (SDF)-1alpha, IL-8), CC (macrophage inflammatory protein (MIP)-1beta, monocyte chemotactic protein (MCP)-2), and C (lymphotactin (Ltn)) subfamilies. BA did not interact with CX3C chemokine fractalkine/neurotactin or other cytokines, such as TNF-alpha and IFN-gamma, indicating that its action is selective. These results suggest that one possible anti-inflammatory mechanism of BA is to bind a variety of chemokines and limit their biological function.

Animals↗

PubMed2000

Opioids suppress chemokine-mediated migration of monkey neutrophils and monocytes - an instant response.

Opioid users having acquired human immunodeficiency syndrome (AIDS) are at a greater risk than non-users of contracting opportunistic infections. Opioid-administered and simian immunodeficiency virus (SIV)-infected rhesus monkeys have been an excellent model for studying AIDS and drug abuse in humans. In this study, chemotaxis of monkey leukocytes was evaluated using the chemokines interleukin-8 (IL-8) and regulated upon activation, normal T cell expressed (RANTES) as the chemoattractants, and the effects of various opioid agonists and antagonists on the efficiency of chemotaxis were examined. Opioids were either incubated with monkey leukocytes or added directly to chemokines, and the number of cells migrating toward IL-8 (for neutrophils) or RANTES (for monocytes) was scored. Inhibition of chemotaxis was seen with both assay conditions, and the inhibition was mediated by opioids binding to mu or kappa receptors. Binding to delta opiod receptors was rarely, if ever, observed. Although opioids themselves may act as weak chemoattractants for monkey leukocytes, addition of opioid agonists to chemokines would reduce the chemoattractant ability of the chemokines. Opioids did not cause the same inhibitory effect on the chemotactic migration of neutrophils when the complement component C5a or the chemotactic peptide N-formyl-MET-LEU-PHE (fMLP) was used as chemoattractant. These studies suggest that the presence of opioids during SIV infection immediately alters chemokine-mediated immune functions.

Animals↗

PubMed2000

Cell cycle-dependent localization of the CDK2-cyclin E complex in Cajal (coiled) bodies.

We have found that CDK2 and cyclin E, but not cyclin A, accumulates within Cajal bodies (CBs) in a cell cycle-dependent fashion. In the absence of cyclin E, CDK2 is not enriched in the CB compartment, suggesting that the translocation of CDK2 to CBs is dependent on cyclin E. CDK2 and cyclin E could be recruited to CBs as a functional complex or CBs may serve as 'docking stations' for CDK2-cyclin E activation by CAKs during the G(1)/S transition. Notably, CDK7-cyclin H-Mat1 complexes are known to accumulate in CBs. Treatment of cells with inhibitors of either CDKs (olomoucine, 200 microM) or RNA polymerase I (actinomycin D, 0.05 microgram/ml), results in a striking reorganization of CDK2 and p80 coilin to the nucleolar periphery. Furthermore, we demonstrate that p80 coilin can be phosphorylated by purified CDK2-cyclin E complexes in vitro. Thus coilin and other CB proteins appear to be downstream targets of CDK2-cyclin E complex-mediated signaling pathways regulating cell cycle progression and controlling aspects of CB function. Possible roles for CDK2 and cyclin E in the well-documented association of CBs, histone gene clusters and RNA 3' end processing factors are discussed.

Animals↗

PubMed1998

Isolation and characterization of a bovine neural specific protein (CRMP-2) cDNA homologous to unc-33, a C. elegans gene implicated in axonal outgrowth and guidance.

We have cloned the cDNA encoding bovine CRMP-2 from bovine brains. A full length cDNA encoding bovine CRMP-2 was isolated and sequenced. The deduced amino acid sequence reveals that the gene encodes a protein of 572 amino acids and is highly homologous to Caenorhabditis elegans unc-33, which controls the guidance and outgrowth of neuronal axons. The CRMP-2 transcript was present in bovine brains but not non-neural tissues, and its protein product existed in both soluble and membrane-bound forms. The expression of CRMP-2 protein and mRNA was upregulated during neuronal differentiation of rat PC12 cells. Immunoprecipitation of PC12 cell extracts shows that CRMP-2 was co-immunoprecipitated with a 190 kDa protein (p190). Both CRMP-2 and p190 were phosphorylated on serine residues in vivo and in vitro in a kinase assay of CRMP-2 immune complexes. Immunocytochemistry shows that CRMP-2 was exclusively localized in both the central and peripheral nervous systems in mouse embryos and detectable in the adult brain although the level of CRMP-2 decreased. The protein was expressed in the axon, dendrite, and cytoplasm of postmitotic neurons and in the cytoplasm of oligodendrocytes and astrocytes. The CRMP-2 gene maps to the region of mouse chromosome 14 syntenic with human chromosome 8p21. Taken together, these data suggest multi-functional roles for CRMP-2 in developing and adult nervous systems, and the biological activity of CRMP-2 could be regulated by phosphorylation reaction.

Amino Acid Sequence↗

PubMed1997

Studies on the role of fibroblast growth factor signaling in neurogenesis using conjugated/aged animal caps and dorsal ectoderm-grafted embryos.

Basic fibroblast growth factor (bFGF) has been shown to induce neural fate in dissociated animal cap (AC) cells or in AC explants cultured in low calcium and magnesium concentrations. However, long-term disclosure of the cap may cause diffusion of the secreted molecule bone morphogenetic protein 4 (BMP-4), a neural inhibitor present in the AC. This may contribute to the subsequent neurogenesis induced by bFGF. Here we used conjugated and aged blastula AC to avoid diffusion of endogenous molecules from the AC. Unlike noggin, bFGF failed to induce neural tissue in this system. However, it enhanced neuralization elicited by a dominant negative BMP receptor (DN-BR) that inhibits the BMP-4 signaling. Posterior neural markers were turned on by bFGF in AC expressing DN-BR or chordin. Blocking the endogenous FGF signal with a dominant negative FGF receptor (XFD) mainly inhibited development of posterior neural tissue in neuralized ACs. These in vitro studies were confirmed in vivo in embryos grafted with XFD-expressing ACs in the place of neuroectoderm. Expression of some regional neural markers was inhibited, although markers for muscle and posterior notochord were still detectable in the grafted embryos, suggesting that XFD specifically affected neurogenesis but not the dorsal mesoderm. The use of these in vitro and in vivo model systems provides new evidence that FGF, although unable to initiate neurogenesis on its own, is required for neural induction as well as for posteriorization.

Animals↗

PubMed1997

Malignant transformation of mammalian cells initiated by constitutive expression of the polo-like kinase.

Polo-like kinase (Plk) is the mammalian homologue of the Drosophila polo and Saccharomyces cerevisiae CDC5 genes, which are thought to be involved in regulating chromosomal segregation. Previously, we showed that transient ectopic expression of Plk could induce DNA synthesis in quiescent NIH 3T3 cells, suggesting that Plk might also have a function during G1 or S phase. Here we report that microinjection of Plk mRNA is sufficient to drive quiescent cells into mitosis and that constitutive expression of Plk in NIH 3T3 cells causes oncogenic focus formation. These transformed cells grow in soft agar and form tumors in nude mice. Because Plk expression has been shown to be high in various human tumors, we suggest that Plk may contribute to the promotion and/or progression of human cancers.

3T3 Cells↗

PubMed1997

The Kinetic Significance of V5 in n-Butane Oxidation Catalyzed by Vanadium Phosphates

Maleic anhydride, a precursor to polyester resins, is made by oxidation of n-butane over vanadium phosphate catalysts. This system is of general interest because it is the only heterogeneously catalyzed, alkane-selective oxidation reaction in commercial use. Time-resolved in situ x-ray absorption spectroscopy shows that when either alphaI-VOPO4/SiO2 or (VO)2P2O7/SiO2 catalysts are exposed to n-butane, the rate of maleic anhydride formation is proportional to the rate of decay of V5+ species in the catalyst. Thus V5+ species are kinetically significant for the production of maleic anhydride and not just for the production of by-products. The results also suggest that V5+ species may play a role in the initial hydrogen abstraction from n-butane, the rate-determining step in the reaction sequence. V4+ sites appear to be responsible for by-product formation.

Journal Article↗

PubMed1997

TIMP-3 induces cell death by stabilizing TNF-alpha receptors on the surface of human colon carcinoma cells.

Matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases (TIMPs) regulate the structural integrity of the extracellular matrix (ECM). Constitutive expression of human TIMP-3 in human DLD colon carcinoma cells renewed serum-responses and inhibited tumour formation in nude mice. To elucidate the mechanism of TIMP-3-mediated tumour suppression, we compared parental DLD and TIMP-3 expressing DLD cells (TIMP-3/DLD), finding them to be significantly different. TIMP-3/DLD cultures have fewer mitotic cells, are delayed in G1, and die after serum starvation. TIMP-3/DLD conditioned media activates cell death on fibroblast cells. The cell death induced by serum starvation and conditioned media was inhibited by 70%, in the presence of neutralizing tumour necrosis factor alpha (TNF-alpha) antibody. TIMP-3/DLD whole cell lysate contained p55 TNF-alpha receptor, while vector/DLD lysate had p55 TNF-alpha receptor and p46 soluble TNF-alpha inhibitor. Vector/DLD conditioned media had p46, while no soluble TNF-alpha receptor was detected in TIMP-3/DLD conditioned media. In addition, FACS analysis revealed that TIMP-3/DLD cells have more TNF-alpha surface binding sites, suggesting a direct correlation between TIMP-3 expression and surface receptors. The mechanism of tumorigenic reversion induced by TIMP-3 in DLD cells may involve protection of receptors from the proteolytic activity of MMPs. Putative TIMP-3-mediated inhibition of MMPs restores the TNF-alpha p55 signalling pathway and the carcinoma cell is killed by autocrine TNF-alpha. Thus, DLD cells have specific ECM MMPs that cleave cytokines and cytokine receptors. TIMP-3 specifically inhibits MMPs involved in receptor shedding.

Antigens, CD↗

PubMed1997

XBMP-1B (Xtld), a Xenopus homolog of dorso-ventral polarity gene in Drosophila, modifies tissue phenotypes of ventral explants.

Previously we have isolated a Xenopus cDNA homolog of bone morphogenetic protein-1 (XBMP-1A). In the present report we describe a new cDNA clone called XBMP-1B (or Xtld) from a Xenopus embryonic library. Sequence analysis indicates that these two clones share an indentical N-terminal sequence, including a region of metalloprotease domain, three copies of a repeat first found in complement proteins C1r/s and an epidermal growth factor (EGF)-like sequence. XBMP-1B protein has an additional copy of an EGF-like sequence followed by two copies of complement 1 r/s repeat in the C-terminus. The overall protein structure predicted from the XBMP-1B sequence reveals that it encodes a protein homologous to Drosophila tolloid. Three XBMP-1 transcripts (2.9, 5.2 and 6.6 kb) were detected by northern blot analysis. However, the 2.9 kb transcript hybridized specifically with XBMP-1A and the 5.2 and 6.6 kb transcripts hybridized with XBMP-1B. In Drosophila, a major function of tolloid is to augment the activity of the decapentaplegic gene product, a close relative of tumor growth factor (TGF)-beta superfamily members, BMP-2/4. Although XBMP-1 and XBMP-4 are detected in various adult tissues of Xenopus, the expression pattern of these two genes was not tightly correlated. In the embryo, the expression of XBMP-1 increased gradually from the morula to the swimming tadpole stages. Injection of XBMP-1B RNA into the ventral blastomeres at the 4-cell stage caused an elongation of the ventral marginal zone explants and converted globin-positive blood cells to mesenchymal and muscle tissues at later stages. It was shown that XBMP-1A was less active and a 1A mutant lacking the signal sequence was inactive. Further studies revealed that injection of XBMP-1B RNA into the ventral marginal zone induced up-regulation of dorsal marginal zone markers, such as goosecoid and chordin, at the gastrulation stage. These data indicate that XBMP-1 may have a role in determining dorso-ventral patterning in Xenopus, but in a different way from the dpp/tolloid system demonstrated in Drosophila.

Amino Acid Sequence↗

PubMed1997

Xmsx-1 modifies mesodermal tissue pattern along dorsoventral axis in Xenopus laevis embryo.

This study analyzes the expression and the function of Xenopus msx-1 (Xmsx-1) in embryos, in relation to the ventralizing activity of bone morphogenetic protein-4 (BMP-4). Expression of Xmsx-1 was increased in UV-treated ventralized embryos and decreased in LiCl-treated dorsalized embryos at the neurula stage (stage 14). Whole-mount in situ hybridization analysis showed that Xmsx-1 is expressed in marginal zone and animal pole areas, laterally and ventrally, but not dorsally, at mid-gastrula (stage 11) and late-gastrula (stage 13) stages. Injection of BMP-4 RNA, but not activin RNA, induced Xmsx-1 expression in the dorsal marginal zone at the early gastrula stage (stage 10+), and introduction of a dominant negative form of BMP-4 receptor RNA suppressed Xmsx-1 expression in animal cap and ventral marginal zone explants at stage 14. Thus, Xmsx-1 is a target gene specifically regulated by BMP-4 signaling. Embryos injected with Xmsx-1 RNA in dorsal blastomeres at the 4-cell stage exhibited a ventralized phenotype, with microcephaly and swollen abdomen. Histological observation and immunostaining revealed that these embryos had a large block of muscle tissue in the dorsal mesodermal area instead of notochord. On the basis of molecular marker analysis, however, the injection of Xmsx-1 RNA did not induce the expression of alpha-globin, nor reduce cardiac alpha-actin in dorsal marginal zone explants. Furthermore, a significant amount of alpha-actin was induced and alpha-globin was turned off in the ventral marginal zone explants injected with Xmsx-1. These results indicated that Xmsx-1 is a target gene of BMP-4 signaling, but possesses a distinct activity on dorsal-ventral patterning of mesodermal tissues.

Animals↗

PubMed1996

AP-1/jun is required for early Xenopus development and mediates mesoderm induction by fibroblast growth factor but not by activin.

In Xenopus, normal mesoderm formation depends on signaling through the fibroblast growth factor (FGF) tyrosine kinase receptor. An important signaling pathway from receptor tyrosine kinases involves Ras/Raf/MAP kinase. However, the downstream pathway that occurs in the nucleus to finally trigger gene expression for mesoderm formation remains unknown. We report here that a high level of activator protein-1 (AP-1)-dependent transcriptional activity is detected during the early development of Xenopus embryos. Injection of a dominant negative mutant jun (DNM-jun or TAM67) RNA into the two-cell stage embryos inhibited endogenous AP-1 activity and blocked normal embryonic development with severe posterior truncation in tadpoles. The inhibition of AP-1 activity and the phenotypic change induced by TAM67 was rescued by co-injection of wild-type c-jun RNA, but not by the control beta-galactosidase RNA. The FGF-stimulated mesoderm induction was markedly inhibited in animal cap explants from the embryos injected with TAM67. Activin induction of mesoderm, on the other hand, was normal in the embryos injected with TAM67 RNA. These findings suggest that AP-1 mediates FGF, but not activin, receptor signaling during mesoderm induction and the AP-1/Jun is a key signaling molecule in the development of posterior structure.

Activins↗

PubMed1996

Catalytic activity of the mouse guanine nucleotide exchanger mSOS is activated by Fyn tyrosine protein kinase and the T-cell antigen receptor in T cells.

mSOS, a guanine nucleotide exchange factor, is a positive regulator of Ras. Fyn tyrosine protein kinase is a potential mediator in T-cell antigen receptor signal transduction in subsets of T cells. We investigated the functional and physical interaction between mSOS and Fyn in T-cell hybridoma cells. Stimulation of the T-cell antigen receptor induced the activation of guanine nucleotide exchange activity in mSOS immunoprecipitates. Overexpression of Fyn mutants with an activated kinase mutation and with a Src homology 2 deletion mutation resulted in a stimulation and suppression of the mSOS activity, respectively. The complex formations of Fyn-Shc, Shc-Grb2, and Grb2-mSOS were detected in the activated Fyn-transformed cells, whereas the SH2 deletion mutant of Fyn failed to form a complex with mSOS. Moreover, tyrosine phosphorylation of Shc was induced by the overexpression of the activated Fyn. These findings support the idea that Fyn activates the activity of mSOS bound to Grb2 through tyrosine phosphorylation of Shc. Unlike the current prevailing model, Fyn-induced activation of Ras might involve the stimulation of the catalytic guanine nucleotide exchange activity of mSOS.

Adaptor Proteins, Signal Transducing↗

PubMed1995

Tat mediates transcriptional activation of HIV-1 gene in vitro.

Gene expression of human immunodeficiency virus (HIV-1) is greatly enhanced by a viral transactivator, the Tat protein, which interacts with R region sequences of the HIV-1 long terminal repeat (LTR). There is no direct evidence to indicate transcriptional activation of HIV-1 by Tat. Using an in vitro transcription system, we demonstrate that an established mouse cell line, which constitutively expresses Tat protein, selectively stimulates the steady state levels of the transcripts directed from the long terminal repeat (LTR) sequences of HIV-1. The gel binding retardation assays further demonstrate a stable activated complex, formed due to direct binding of Tat to DNA elements of the HIV-1 LTR. These data implicate transcription as the site of Tat action in trans-activation and could play an essential role in human immunodeficiency virus replication, similar to the nuclear trans-activators of other viruses.

Animals↗