Zoumpourlis

Bio: Zoumpourlis is an academic researcher. The author has contributed to research in topics: Gene & Long terminal repeat. The author has an hindex of 4, co-authored 5 publications receiving 35 citations.

Response of human immunodeficiency virus long terminal repeat to growth factors and hormones.

Abstract: We have employed a recombinant plasmid, pBHIV1, carrying the long terminal repeat (LTR) of the human immunodeficiency virus-1 (HIV-1) linked to the reporter chloramphenicol acetyl transferase (cat) gene and to the aminoglycoside phosphotransferase (aph) gene as a selectable marker. We have introduced pBHIV1 in rat 208F and human MRCSV40TGR fibroblasts and obtained stable geneticin resistant RFBHIV1-1 and SVTGHIV-1 transfectant cells respectively. Both RFBHIV1-1 and SVTGHIV1-1 cells express CAT activity from the HIV LTR promoter. The response to insulin, epidermal growth factor, hydrocortisone and dexamethasone was studied on the LTR regulated CAT activity in both cell lines. It was found that, at optimal concentrations, insulin, epidermal growth factor and hydrocortisone regulate positively the expression of CAT from the HIV LTR in rat RFBHIV1-1 but not in human SVTGHIV1-1 cells. On the other hand dexamethasone at 10(-5) M stimulated CAT activity in both types of cells.

Hexamethylene bisacetamide stimulates the expression of human immunodeficiency virus long terminal repeat sequences in rat and human fibroblasts.

Abstract: We have employed a recombinant plasmid, pBHIV1, carrying the long terminal repeat (LTR) sequence of the human immunodeficiency virus-1 (HIV-1) linked to the reporter chloramphenicol acetyl transferase (CAT) gene and to the aminoglycoside phosphotransferase (aph) gene as a selectable marker. We have introduced pBHIV1 in rat 208F and human MRCSV40TGR fibroblasts and obtained stable geneticin resistant RFBHIV1-1 and SVTGHIV1-1 cells, respectively. Both transfectant cells express CAT activity from the HIV LTR promoter. The response to anti-neoplastic drug hexamethylene bisacetamide (HMBA) was studied on the LTR regulated CAT activity in both cell lines. It was found that HMBA at 5mM concentration stimulates the expression of CAT from the HIV LTR in rat and human cells by 28- and 1.9-fold, respectively.

Binding of the glucocorticoid and estrogen-receptors to the human h-ras oncogene sequences

Abstract: There is evidence that hormone regulation of cellular oncogenes plays an essential role in human cancer. The c-H-ras gene is implicated through both mutation and abnormal gene expression in many types of human cancer. Computer scanning of this gene has revealed two putative hormone response motifs: A possible Glucocorticoid Response Element (GRE) at position 1261 of the first intron of the H-rasl gene and a putative Estrogen Response Element (ERE), at position 3007 of the fourth intron of the gene. In DNA binding assays, using the HeLa and LATK~ cell lines, we showed specific binding of the corresponding receptors at both putative H-ras glucocorticoid and estrogen response sequences, suggesting that hormones could be contributing to H-ras transcriptional regulation through interaction with their corresponding Hormone Response Elements (HREs).

Ap-1 recognizes sequence elements on hiv-1 LTR in human epithelial tumor-cell lines.

Abstract: Investigation of the nucleotide sequence of the HIV-1 LTR showed the presence of four novel short DNA regions which are homologous to the recognition site for the cellular transcription factor AP-1. Four short oligonucleotide hybrids containing these potential AP-1 sites were constructed and used in gel retardation assays and in competition experiments in order to determine the role of the AP-L protein in the regulation of HIV-1 expression. The breast MDA MB 468 and cervical HeLa turner cell lines, which are known to overexpress the AP-1 protein were used in a gel retardation assay as a control to study the affinity of the AP-1 to synthesized oligonucleotide sequences. We have observed specific binding of nuclear factor AP-1 to three of these oligonucleotide hybrids. These results demonstrate the presence of three novel AP-1 binding sites on HIV-1 LTR, one of which was found within the TAR element and in the Tat protein binding region. Moreover, they suggest that AP-1 could be contributing to HIV-1 transcriptional regulation through its interaction with the AP-1 binding sites of HIV-1 LTR.

Human lung, bladder and head and neck tumors as compared to their adjacent normal-tissues have elevated ap-1 activity and recognize sequence elements of hiv-1 LTR.

Abstract: We have previously reported the specific binding of nuclear factor AP-1 isolated from human breast MDA MB 468 and HeLa cervical tumor cell lines to oligonucleotides complementary to three newly elucidated sequences within the HIV-1 LTR These synthesized oligonucleotides, which bear high homology to the AP-1 recognition sequence, were used in the present study in gel retardation assays together with unfractionated nuclear protein extracts from human lung, bladder and head and neck tumors and adjacent normal tissue to study the role of the AP-1 protein in the regulation of HIV-1 expression We found increased binding of AP-1 to these oligonucleotides in 9/12 lung tumors, 9/14 bladder tumors and 7/7 head and neck tumors as compared to adjacent normal tissues This confirms previous results obtained when using MDA MB 468 and HeLa nuclear protein extracts These results indicate that, AP-1 could be contributing to the HIV-1 transcriptional regulation through its interaction with the AP-I binding sites of HIV-I LTR

Psychobiology of HIV infection.

Abstract: This review surveys evidence relevant to the proposition that psychobiologic factors may influence the progress of infection with human immunodeficiency virus Type 1 (HIV-1). Little research has directly examined the influence of psychobiologic factors on the pathogenetic mechanisms underlying HIV progression. However, basic research in neuroimmune interactions indicates that activation of the sympathetic nervous system and hypothalamic-pituitary-adrenal axis can influence several immunologic processes relevant to HIV pathogenesis and the body's ability to resist the progress of infection. A small number of observational natural history studies indicate that certain psychosocial characteristics may be associated with differential disease progression (e.g., subjective responses to highly threatening events, and inhibited psychosocial characteristics). We address some of the methodologic and conceptual issues critical to the interpretation of current results as evidence that psychobiologic processes influence HIV progression, and we conclude by highlighting promising areas for future inquiry.

Estrogen and progesterone receptors in the endometrium.

Abstract: The endometrium, as a target of estrogens and progestins, possesses the respective receptor proteins. These receptors belong to the superfamily of nuclear receptors, having important functional domains required for steroid ligand binding, for dimer formation, for interaction with HREs of DNA, for transcription modulation, for association with other proteins, for intracellular trafficking, and other activities. The mechanism of action of the steroid hormones involves modulation of gene activity through interaction of the hormone-receptor complex with HREs and with other nuclear proteins, but also encompasses nongenomic effects, which accounts for the rapid effects of the steroids on cellular functions. Antihormones-antiestrogen and antiprogestins-compete with their respective hormones for binding sites on the receptor molecules. Some antihormones are partial agonists. The molecular mechanisms underlying the dual behavior of antihormones is under consideration. The concentration of ER and PR in different physiological and pathophysiological states, such as the menstrual cycle, pregnancy, and endometrial cancer, has been determined by biochemical and immuno(cyto)chemical methods. The levels of estrogens and progestins are important regulators of ER and PR gene expression. Estradiol acts as a cell mitogen, inducing key genes involved in replication, and its tumor promoter effect is discussed in this sense, whereas progesterone has reverse effects when compared to estradiol and acts as a differentiation factor. The cross-talk between the endocrine system, growth factors, and neurotransmitters can take place both at the receptor level, involving mainly phosphorylation reactions, and at the gene level, mainly through protein-protein interactions.

Signal-induced Brd4 release from chromatin is essential for its role transition from chromatin targeting to transcriptional regulation

Abstract: Bromodomain-containing protein Brd4 is shown to persistently associate with chromosomes during mitosis for transmitting epigenetic memory across cell divisions. During interphase, Brd4 also plays a key role in regulating the transcription of signal-inducible genes by recruiting positive transcription elongation factor b (P-TEFb) to promoters. How the chromatin-bound Brd4 transits into a transcriptional regulation mode in response to stimulation, however, is largely unknown. Here, by analyzing the dynamics of Brd4 during ultraviolet or hexamethylene bisacetamide treatment, we show that the signal-induced release of chromatin-bound Brd4 is essential for its functional transition. In untreated cells, almost all Brd4 is observed in association with interphase chromatin. Upon treatment, Brd4 is released from chromatin, mostly due to signal-triggered deacetylation of nucleosomal histone H4 at acetylated-lysine 5/8 (H4K5ac/K8ac). Through selective association with the transcriptional active form of P-TEFb that has been liberated from the inactive multi-subunit complex in response to treatment, the released Brd4 mediates the recruitment of this active P-TEFb to promoter, which enhances transcription at the stage of elongation. Thus, through signal-induced release from chromatin and selective association with the active form of P-TEFb, the chromatin-bound Brd4 switches its role to mediate the recruitment of P-TEFb for regulating the transcriptional elongation of signal-inducible genes.

Glucocorticoid receptor-binding site in the human immunodeficiency virus long terminal repeat

Abstract: Previous reports (P D Katsanakis, C E Sekaris, and D A Spandidos, Anticancer Res 11:381-383, 1991; J Laurence, M B Sellers, and S K Sikder, Blood 74:291-297, 1989; R Miksicek, A Heber, W Schmid, U Danesch, G Posseckert, M Beato, and G Schutz, Cell 46:283-290, 1986) have suggested the existence of a glucocorticoid response element in the long terminal repeat of human immunodeficiency virus (HIV) type 1 This study demonstrated a sequence-specific interaction of the glucocorticoid receptor DNA-binding domain with the previously predicted HIV glucocorticoid response element This interaction may be relevant to the steroid responsiveness of HIV (P A Furth, H Westphal, and L Hennighausen, AIDS Res Hum Retroviruses 6:553-560, 1990; J Laurence, M B Sellers, and S K Sikder, Blood 74:291-297, 1989; J Laurence, H Cooke, and S K Sikder, Blood 75:696-703, 1990; D A Spandidos, V Zoounpovilis, A Kotsinas, C Tsiripotis, and C E Sekeris, Anticancer Res 10:1241-1246, 1990)

Expression of ras proto-oncogenes: regulation and implications in the development of human tumors

Abstract: 2. Transcriptional regulation of the human c-H-rasl gene 66 2.1. Regulation of the H-ras gene expression from promoter-like sequences 66 2.2. Regulation of the H-ras gene expression from intronic sequences 67 2.3. The role of the VTR in expression of the H-ras gene 68 2.4. DNA methylation affecting H-ras gene expression. 68 2.5. Expression of the H-ras proto-oncogene is controlled by alternative splicing. 68