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1. Differential Regulation of the c-MYC P1 and P2 Promoters in the Absence of Functional Tumor Suppressors: Implications for Mechanisms of Deregulated MYC Transcription

Author

Marcu, K. B., Patel, A. J., Yang, Y., Compans, R. W., editor, Cooper, M., editor, Hogle, J. M., editor, Koprowski, H., editor, Ito, Y., editor, Melchers, F., editor, Oldstone, M., editor, Olsnes, S., editor, Potter, M., editor, Saedler, H., editor, Vogt, P. K., editor, Wagner, H., editor, Potter, Michael, editor, and Melchers, Fritz, editor

Published
1997
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2. The c-myc Story: Where we’ve been, Where we seem to be Going

Author

Potter, M., Marcu, K. B., Compans, R. W., editor, Cooper, M., editor, Hogle, J. M., editor, Koprowski, H., editor, Ito, Y., editor, Melchers, F., editor, Oldstone, M., editor, Olsnes, S., editor, Potter, M., editor, Saedler, H., editor, Vogt, P. K., editor, Wagner, H., editor, Potter, Michael, editor, and Melchers, Fritz, editor

Published
1997
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3. Chromosomally Integrated Retroviral Substrates are Sensitive Indicators of an Antibody Class Switch Recombinase-Like Activity

Author

Ballantyne, J., Ozsvath, L., Bondarchuk, K., Marcu, K. B., Capron, A., editor, Compans, R. W., editor, Cooper, M., editor, Koprowski, H., editor, McConnell, I., editor, Melchers, F., editor, Oldstone, M., editor, Olsnes, S., editor, Potter, Michael, editor, Saedler, H., editor, Vogt, P. K., editor, Wagner, H., editor, Wilson, I., editor, and Melchers, Fritz, editor

Published
1995
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4. Cloning and Characterization of DNA Binding Factors Which Bind Sequences Required for Proper c-myc Initiation

Author

Bossone, S. A., Patel, A. J., Asselin, C., Marcu, K. B., Capron, A., editor, Compans, R. W., editor, Cooper, M., editor, Koprowski, H., editor, McConnell, I., editor, Melchers, F., editor, Oldstone, M., editor, Olsnes, S., editor, Potter, M., editor, Saedler, H., editor, Vogt, P. K., editor, Wagner, H., editor, Wilson, I., editor, Potter, Michael, editor, and Melchers, Fritz, editor

Published
1992
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5. PCS, a Gene Related to the Immunoglobulin Super Family of Axonal Glycoproteins is Expressed in Murine Plasma Cell Tumors

Author

Connelly, M. A., Grady, R. C., Mushinski, J. F., Marcu, K. B., Capron, A., editor, Compans, R. W., editor, Cooper, M., editor, Koprowski, H., editor, McConnell, I., editor, Melchers, F., editor, Oldstone, M., editor, Olsnes, S., editor, Potter, M., editor, Saedler, H., editor, Vogt, P. K., editor, Wagner, H., editor, Wilson, I., editor, Potter, Michael, editor, and Melchers, Fritz, editor

Published
1992
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6. SαBP/BSAP/NF-Sμ B1, a Murine and Human B Cell Stage Specific Nuclear Factor with DNA Binding Specificity Implying Roles in Switch-Recombination and Transcription

Author

Marcu, K. B., Xu, L., Kim, M. G., Capron, A., editor, Compans, R. W., editor, Cooper, M., editor, Koprowski, H., editor, McConnell, I., editor, Melchers, F., editor, Oldstone, M., editor, Olsnes, S., editor, Potter, M., editor, Saedler, H., editor, Vogt, P. K., editor, Wagner, H., editor, Wilson, I., editor, Potter, Michael, editor, and Melchers, Fritz, editor

Published
1992
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9. Negative Control Elements Within and Near the Murine c-myc Gene

Author

Marcu, K. B., Asselin, C., Nepveu, A., Weisinger, G., Yang, J. Q., Compans, R. W., editor, Cooper, M., editor, Koprowski, H., editor, McConell, I., editor, Melchers, F., editor, Oldstone, M., editor, Olsnes, S., editor, Saedler, H., editor, Vogt, P. K., editor, Wagner, H., editor, Wilson, I., editor, Potter, Michael, editor, and Melchers, Fritz, editor

Published
1988
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10. Synergy of an IgH Promoter-Enhancer-Driven c-myc/v-Ha-ras Retrovirus and Pristane in the Induction of Murine Plasmacytomas

Author

Clynes, R., Stanton, L. W., Wax, J., Smith-Gill, S., Potter, M., Marcu, K. B., Compans, R. W., editor, Cooper, M., editor, Koprowski, H., editor, McConell, I., editor, Melchers, F., editor, Oldstone, M., editor, Olsnes, S., editor, Saedler, H., editor, Vogt, P. K., editor, Wagner, H., editor, Wilson, I., editor, Potter, Michael, editor, and Melchers, Fritz, editor

Published
1988
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11. Biological Effects of High Level c-myc Expression in FR3T3 Fibroblasts

Author

Zerlin, M., Julius, M. A., Cerni, C., Marcu, K. B., Clarke, A., editor, Compans, R. W., editor, Cooper, M., editor, Eisen, H., editor, Goebel, W., editor, Koprowski, H., editor, Melchers, F., editor, Oldstone, M., editor, Vogt, P. K., editor, Wagner, H., editor, Wilson, I., editor, Melchers, Fritz, editor, and Potter, Michael, editor

Published
1986
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12. Studies on c-myc Regulation in Normal and Transformed Cells

Author

Marcu, K. B., Fahrlander, P. D., Julius, M. A., Nepveu, A., Remmers, E. F., Yang, J. Q., Clarke, A., editor, Compans, R. W., editor, Cooper, M., editor, Eisen, H., editor, Goebel, W., editor, Koprowski, H., editor, Melchers, F., editor, Oldstone, M., editor, Vogt, P. K., editor, Wagner, H., editor, Wilson, I., editor, Melchers, Fritz, editor, and Potter, Michael, editor

Published
1986
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13. c-myc and Functionally Related Oncogenes Induce Both High Rates of Sister Chromatid Exchange and Abnormal Karyotypes in Rat Fibroblasts

Author

Cerni, C., Mougneau, E., Zerlin, M., Julius, M., Marcu, K. B., Cuzin, F., Clarke, A., editor, Compans, R. W., editor, Cooper, M., editor, Eisen, H., editor, Goebel, W., editor, Koprowski, H., editor, Melchers, F., editor, Oldstone, M., editor, Vogt, P. K., editor, Wagner, H., editor, Wilson, I., editor, Melchers, Fritz, editor, and Potter, Michael, editor

Published
1986
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14. Mutations which Stabilize myc Transcripts and Enhance myc Transcription in Two Mouse Plasmacytomas

Author

Bauer, S. R., Piechaczyk, M., Marcu, K. B., Nordan, R. P., Potter, M., Mushinski, J. F., Clarke, A., editor, Compans, R. W., editor, Cooper, M., editor, Eisen, H., editor, Goebel, W., editor, Koprowski, H., editor, Melchers, F., editor, Oldstone, M., editor, Vogt, P. K., editor, Wagner, H., editor, Wilson, I., editor, Melchers, Fritz, editor, and Potter, Michael, editor

Published
1986
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15. Altered c-myc RNA Metabolism in Burkitt’s Lymphomas and Mouse Plasmacytomas

Author

Piechaczyk, M., Bonnieu, A., Eick, D., Remmers, E., Yang, J-Q., Marcu, K., Jeanteur, Ph., Blanchard, J-M, Clarke, A., editor, Compans, R. W., editor, Cooper, M., editor, Eisen, H., editor, Goebel, W., editor, Koprowski, H., editor, Melchers, F., editor, Oldstone, M., editor, Vogt, P. K., editor, Wagner, H., editor, Wilson, I., editor, Melchers, Fritz, editor, and Potter, Michael, editor

Published
1986
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16. Modes of c-myc Oncogene Activation in Murine Plasmacytomas

Author

Yang, J. Q., Mushinski, J. F., Stanton, L. W., Fahrlander, P. D., Tesser, P. C., Marcu, K. B., Cooper, M., editor, Goebel, W., editor, Hofschneider, P. H., editor, Koprowski, H., editor, Melchers, F., editor, Oldstone, M., editor, Rott, R., editor, Schweiger, H. G., editor, Vogt, P. K., editor, Zinkernagel, R., editor, Potter, Michael, editor, Melchers, Fritz, editor, and Weigert, Martin, editor

Published
1984
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17. Aberrant Igh Locus Rearrangements in A-MuLV pre B Lines of scid Mice: Evidence for Deregulated D-J Recombination

Author

Kim, M. G., Schuler, W., Bosma, M. J., Marcu, K. B., Clarke, A., editor, Compans, R. W., editor, Cooper, M., editor, Eisen, H., editor, Goebel, W., editor, Koprowski, H., editor, Melchers, F., editor, Oldstone, M., editor, Vogt, P. K., editor, Wagner, H., editor, Wilson, I., editor, Mock, Beverly, editor, and Potter, Michael, editor

Published
1988
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18. The Genetics of Susceptibility to RIM-Induced Plasmacytomagenesis

Author

Mock, B., Wax, J., Clynes, R., Marcu, K. B., Potter, M., Compans, R. W., editor, Cooper, M., editor, Koprowski, H., editor, McConell, I., editor, Melchers, F., editor, Oldstone, M., editor, Olsnes, S., editor, Saedler, H., editor, Vogt, P. K., editor, Wagner, H., editor, Wilson, I., editor, Potter, Michael, editor, and Melchers, Fritz, editor

Published
1988
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19. Regulated transcription of human matrix metalloproteinase 13 (MMP13) and interleukin-1β (IL1B) genes in chondrocytes depends on methylation of specific proximal promoter CpG sites

Author

Hashimoto, K., Otero, M., Imagawa, K., De Andrés González, Mª Carmen, Coico, J. M., Roach, H. I., Oreffo, R. O. C., Marcu, K. B., and Goldring, M. B.

Subjects
Transcriptional Activation, Models, Genetic, Gene Expression Profiling, Interleukins, Interleukin-1beta, Sequence Analysis, DNA, DNA Methylation, Gene Expression Regulation, Enzymologic, Epigenesis, Genetic, Cartilage, Matrix Metalloproteinase 13, Osteoarthritis, Humans, Point Mutation, CpG Islands, Promoter Regions, Genetic, Plasmids
Abstract

The role of DNA methylation in the regulation of catabolic genes such as MMP13 and IL1B, which have sparse CpG islands, is poorly understood in the context of musculoskeletal diseases. We report that demethylation of specific CpG sites at -110 bp and -299 bp of the proximal MMP13 and IL1B promoters, respectively, detected by in situ methylation analysis of chondrocytes obtained directly from human cartilage, strongly correlated with higher levels of gene expression. The methylation status of these sites had a significant impact on promoter activities in chondrocytes, as revealed in transfection experiments with site-directed CpG mutants in a CpG-free luciferase reporter. Methylation of the -110 and -299 CpG sites, which reside within a hypoxia-inducible factor (HIF) consensus motif in the respective MMP13 and IL1B promoters, produced the most marked suppression of their transcriptional activities. Methylation of the -110 bp CpG site in the MMP13 promoter inhibited its HIF-2alpha-driven transactivation and decreased HIF-2alpha binding to the MMP13 proximal promoter in chromatin immunoprecipitation assays. In contrast to HIF-2alpha, MMP13 transcriptional regulation by other positive (RUNX2, AP-1, ELF3) and negative (Sp1, GATA1, and USF1) factors was not affected by methylation status. However, unlike the MMP13 promoter, IL1B was not susceptible to HIF-2alpha transactivation, indicating that the -299 CpG site in the IL1B promoter must interact with other transcription factors to modulate IL1B transcriptional activity. Taken together, our data reveal that the methylation of different CpG sites in the proximal promoters of the human MMP13 and IL1B genes modulates their transcription by distinct mechanisms.

Published
2013

24. Chronic NF-kappaB activation delays RasV12-induced premature senescence of human fibroblasts by suppressing the DNA damage checkpoint response

Author

Batsi, C., Markopoulou, S., Vartholomatos, G., Georgiou, I., Kanavaros, P., Gorgoulis, V. G., Marcu, K. B., and Kolettas, E.

Subjects
NF-kappa B/genetics/*metabolism, Tumor Suppressor Protein p53/genetics/metabolism, DNA Damage, Fibroblasts/cytology/*metabolism, Oncogene Protein p21(ras)/genetics/*metabolism, Humans, Cyclin-Dependent Kinase Inhibitor p21/genetics/metabolism, Cell Aging, Cells, Cultured, Signal Transduction, Cell Proliferation
Abstract

Normal cells divide for a limited number of generations, after which they enter a state of irreversible growth arrest termed replicative senescence. While replicative senescence is due to telomere erosion, normal human fibroblasts can undergo stress-induced senescence in response to oncogene activation, termed oncogene-induced senescence (OIS). Both, replicative and OIS, initiate a DNA damage checkpoint response (DDR) resulting in the activation of the p53-p21(Cip1/Waf1) pathway. However, while the nuclear factor-kappaB (NF-kappaB) signaling pathway has been implicated in DDR, its role in OIS has not been investigated. Here, we show that oncogenic Ha-RasV12 promoted premature senescence of IMR-90 normal human diploid fibroblasts by activating DDR, hence verifying the classical model of OIS. However, enforced expression of a constitutively active IKKbeta T-loop mutant protein (IKKbetaca), significantly delayed OIS of IMR-90 cells by suppressing Ha-RasV12 instigated DDR. Thus, our experiments have uncovered an important selective advantage in chronically activating canonical NF-kappaB signaling to overcome the anti-proliferative OIS response of normal primary human fibroblasts. Mech Ageing Dev

Published
2009

25. Bcl-2 blocks 2-methoxyestradiol induced leukemia cell apoptosis by a p27(Kip1)-dependent G1/S cell cycle arrest in conjunction with NF-kappaB activation

Author

Batsi, C., Markopoulou, S., Kontargiris, E., Charalambous, C., Thomas, C., Christoforidis, S., Kanavaros, P., Constantinou, A. I., Marcu, K. B., and Kolettas, E.

Subjects
S Phase/drug effects/*physiology, Jurkat Cells/cytology/*drug effects, Estradiol/*analogs & derivatives/pharmacology, Cyclin-Dependent Kinase Inhibitor p27/genetics, Cyclin-Dependent Kinase Inhibitor p21/genetics, Humans, G1 Phase/drug effects/*physiology, Apoptosis/*drug effects, Cell Cycle/drug effects/genetics, Cyclin-Dependent Kinases/antagonists & inhibitors, NF-kappa B/*physiology, Proto-Oncogene Proteins c-bcl-2/*physiology
Abstract

2-Methoxyestradiol (2-ME2) induces leukemia cells to undergo apoptosis in association with Bcl-2 inactivation but the mechanisms whereby Bcl-2 contributes to protection against programmed cell death in this context remain unclear. Here we showed that 2-ME2 inhibited the proliferation of Jurkat leukemia cells by markedly suppressing the levels of cyclins D3 and E, E2F1 and p21(Cip1/Waf1) and up-regulating p16(INK4A). Further, 2-ME2 induced apoptosis of Jurkat cells in association with down-regulation and phosphorylation of Bcl-2 (as mediated by JNK), up-regulation of Bak, activation of caspases-9 and -3 and PARP-1 cleavage. To determine the importance and mechanistic role of Bcl-2 in this process, we enforced its expression in Jurkat cells by retroviral transduction. Enforcing Bcl-2 expression in Jurkat cells abolished 2-ME2-induced apoptosis and instead produced a G1/S phase cell cycle arrest in association with markedly increased levels of p27(Kip1). Bcl-2 and p27(Kip1) were localized mainly in the nucleus in these apoptotic resistant cells. Interestingly, NF-kappaB activity and p50 levels were increased by 2-ME2 and suppression of NF-kappaB signaling reduced p27(Kip1) expression and sensitized cells to 2-ME2-induced apoptosis. Importantly, knocking-down p27(Kip1) in Jurkat Bcl-2 cells sensitized them to spontaneous and 2-ME2-induced apoptosis. Thus, Bcl-2 prevented the 2-ME2-induced apoptotic response by orchestrating a p27(Kip1)-dependent G1/S phase arrest in conjunction with activating NF-kappaB. Thus, we achieved a much better understanding of the penetrance and mechanistic complexity of Bcl-2 dependent anti-apoptotic pathways in cancer cells and why Bcl-2 inactivation is so critical for the efficacy of apoptosis and anti-proliferative inducing drugs like 2-ME2. Biochem Pharmacol

Published
2009

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