Induction of transcription factor AP-1 by adenovirus E1A protein and cAMP.

Müller, Ulrich; Roberts, M P; Engel, Daniel A.; Doerfler, Walter; Shenk, Thomas

doi:10.1101/gad.3.12a.1991

Cited by 67 publications

(67 citation statements)

References 67 publications

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“…Some mitotic stimuli, such as phorbol esters and growth factors, activate AP-1 through the protein kinase C (PKC) pathway, while other reagents, such as transforming growth factor (TGF) and cyclic AMP, seem to control AP-1 independently of PKC (Muller et al, 1989). Inhibition of protein kinase activity was performed with GF109203X, staurosporine, HA1004 and H7.…”

Section: Protein Kinase Inhibitors Suppress Ie1 Activation Of Ap-1 Inmentioning

confidence: 99%

Human cytomegalovirus IE1 protein activates AP-1 through a cellular protein kinase(s).

Kim¹,

Lee

et al. 1999

Journal of General Virology

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Section: Protein Kinase Inhibitors Suppress Ie1 Activation Of Ap-1 Inmentioning

confidence: 99%

Human cytomegalovirus IE1 protein activates AP-1 through a cellular protein kinase(s).

Kim¹,

Lee

et al. 1999

Journal of General Virology

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“…Possible DNA-binding proteins involved in this activation are c-Fos, Jun B, and NFKB. c-Fos and Jun B synthesis (35,36) and NFKB-binding activities (37) are stimulated by cAMP. c-Fos and Jun B form a heterodimer that activates gene transcription by binding to the ubiquitous AP-1 binding site.…”

Section: Effects Ofelevated Intracellular Camp On Il-iai and Il-imentioning

confidence: 99%

Increased cyclic AMP levels enhance IL-1 alpha and IL-1 beta mRNA expression and protein production in human myelomonocytic cell lines and monocytes.

Sung

Walters²

1991

J. Clin. Invest.

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The effects of increasing intracellular cAMP levels on IL-la and IL-1,8 mRNA expression and IL-1 production in human monocytes and nonlymphoid hematopoietic cell lines were examined. Peripheral monocytes and myelomonocytic cell lines could be stimulated by LPS or phorbol myristate acetate (PMA) to express IL-1 mRNA. Dibutyryl cAMP, 8-bromocAMP, forskolin, cholera toxin, PGEj, and PGE2 synergized with PMA or LPS to increase the accumulation in cell lines of IL-la mRNA by up to 50-fold and that of IL-1j mRNA by 10-to 20-fold compared to LPS or PMA alone. This increase in IL-la and IL-ljB mRNA accumulation was more modest in monocytes. The synergistic stimulation was due to enhanced IL-1 gene transcription rate rather than increased ILi m.RNA stability. Despite this marked increase in I1-i mRNA accumulation, IL-1 protein synthesis in these cells was increased by only twofold. Thus, II-i synthesis in monocytes and myelomonocytic cell lines is under stringent translational control. (J.

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“…Mutants defective in the E3-11.6K protein also exhibit a similar phenotype (54), and thus, this protein may cooperate with E4orf4 in cell killing. Apoptosis is a mechanism used by a number of viruses as the host inflammatory response is diminished, and progeny are protected from host antibodies and proteases because they are released in apoptotic membrane-bound vesicles (reviewed in references 43a and 50).The biological activity of E4orf4 was first revealed through studies showing a synergistic effect on transcription factor AP-1 by E1A products and cyclic AMP (15,16,36). Under these conditions E4orf4 caused a decrease in phosphorylation of both the E1A protein and c-Fos, the latter causing decreased AP-1 transcriptional activity.…”

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Induction of p53-Independent Apoptosis by the Adenovirus E4orf4 Protein Requires Binding to the Bα Subunit of Protein Phosphatase 2A

Marcellus¹,

Chan²,

Paquette³

et al. 2000

J Virol

159

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Previous studies have indicated that the E4orf4 protein of human adenovirus type 2 (Ad2) induces p53-independent apoptosis. We believe that this process may play a role in cell death and viral spread at the final stages of productive infection. E4orf4 may also be of therapeutic value in treating some diseases, including cancer, through its ability to induce apoptosis when expressed individually. The only previously identified biochemical function of E4orf4 is its ability to associate with the B␣ subunit of protein phosphatase 2A (PP2A). We have used a genetic approach to determine the role of such interactions in E4orf4-induced cell death. E4orf4 deletion mutants were of only limited value, as all were highly defective. We found that E4orf4 proteins from most if not all adenovirus serotypes induced cell death, and thus point mutations were introduced that converted the majority of highly conserved residues to alanines. Such mutants were used to correlate B␣-subunit binding, association with PP2A activity, and cell killing following the transfection of appropriate cDNAs into p53-null H1299 or C33A cells. The results indicated that binding of the B␣ subunit is essential for induction of cell death, as every mutant that failed to bind efficiently was totally defective for cell killing. This class of mutations (class I) largely involved residues between amino acids 51 and 89. Almost all E4orf4 mutant proteins that associated with PP2A killed cancer cells at high levels; however, several mutants that associated with significant levels of PP2A were defective for killing (class II). Thus, binding of E4orf4 to PP2A is essential for induction of p53-independent apoptosis, but E4orf4 may possess one or more additional functions required for cell killing.Successful, productive infection of human cells by adenoviruses involves a complex interplay between the induction and suppression of apoptosis (43a). Proteins encoded by early region 1A (E1A) transactivate early viral gene expression and stimulate cells to enter S phase to enhance viral DNA synthesis. One consequence of E1A expression by human adenovirus type 5 (Ad5) is the stabilization of p53 (11, 29) resulting from complex formation with members of either the retinoblastoma tumor suppressor or the p300/CBP families of cell cycle regulators (8, 42). Adenoviruses prevent apoptosis or growth arrest by p53 through the action of two E1B products, the 55-kDa protein that binds to and inhibits p53 (51, 58) and the 19-kDa polypeptide that suppresses apoptosis via a mechanism analogous to the cellular Bcl-2 protein (6, 18). The turnover of p53 is also enhanced through the action of complexes between the Ad5 E1B 55-kDa protein and a product of E4, E4orf6 (13, 41). In addition, E1A enhances cell susceptibility to killing by tumor necrosis factor (14,46,57), an effect that is also inhibited by the E1B 19-kDa protein (38, 40) as well as E3 products (reviewed in reference 53).In previous studies it was noted that E1B-defective Ad5 also induces apoptosis in p53-null cells through the...

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Induction of transcription factor AP-1 by adenovirus E1A protein and cAMP.

Cited by 67 publications

References 67 publications

Human cytomegalovirus IE1 protein activates AP-1 through a cellular protein kinase(s).

Human cytomegalovirus IE1 protein activates AP-1 through a cellular protein kinase(s).

Increased cyclic AMP levels enhance IL-1 alpha and IL-1 beta mRNA expression and protein production in human myelomonocytic cell lines and monocytes.

Induction of p53-Independent Apoptosis by the Adenovirus E4orf4 Protein Requires Binding to the Bα Subunit of Protein Phosphatase 2A

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