Supreme EnLIGHTenment: damage recognition and signaling in the mammalian UV response. (2008)
Herrlich, P., Karin, M., Weiss, C.
Molecular Cell, 29(2008) S.279-90
R Eports, E. Shaulian, M. Karin, Nature Cell Biol, A. Behrens, M. Sibilia, ...
References andN.10 1. R. J.Davis, 239 (2000). 2. E.Shaulian, M.Karin, Nature Cell E131 (2002). 3. D. D. Yang et al., 389, 865 (1997). 4. A.Behrens, M.Sibilia, E. F.Wagner, Nature Genet. 326 (1999)....
Hsu, LC, Park, JM, Zhang, KZ, Luo, JL, Maeda, S, Kaufman, RJ, ...
Macrophages are pivotal constituents of the innate immune system, vital for recognition and elimination of microbial pathogens(1). Macrophages use Toll-like receptors (TLRs) to detect...
Park, J M, Brady, H, Ruocco, M G, Sun, H Y, Williams, D, Lee, S J, ...
The molecular circuitry underlying innate immunity is constructed of multiple, evolutionarily conserved signaling modules with distinct regulatory targets. The MAP kinases and the IKK-NF-B-K...
Schreiber, M, Piu, F, Kolbus, A, Szabowski, A, Möhle-Steinlein, U, Tian, J, ...
No abstract available.
Kallunki, T, Su, B, Tsigelny, I, Sluss, HK, Derijard, B, Moore, G, ...
Lew, D, Brady, H, Klausing, K, Yaginuma, K, Theill, LE, Stauber, C, ...
Birkedale-Hansen, H. [Hrsg.]
Boyle, W.J., Smeal, T., Defize, L.H.K., Angel, P., Woodgett, J.R., Karin, M., ...
Cell, 64(1991) S.573-84
The role of Jun, Fos and the AP-1 complex in cell-proliferation and transformation. (1991)
Biochimica et Biophysica Acta, (1991) S.129-57
Kaina, B., Lohrer, H., Karin, M., Herrlich, P.
Proceedings of the National Academy of Science of the USA, 87(1990) S.2710-14
The Fos and Jun/AP-1 proteins are involved in the downregulation of Fos transcription. (1989)
Schoenthal, A., Buescher, M., Angel, P., Rahmsdorf, H.J., Ponta, H., Hattori, K., ...
Oncogene, 4(1989) S.629-36
Colburn, N.H. [Hrsg.]
Kaina, B., Lohrer, H., Karin, M., Herrlich, P.
SEK Meeting, Heidelberg, 10.-12.April 1989
Karin, M., Imagawa, M., Bodner, M., Chiu, R., Lefevre, Ch., Imbra, R., ...
Ringold, E. [Hrsg.]
Herrlich, P., Jonat, C., Rahmsdorf, H.J., Angel, P., Haslinger, A., Imagawa, M., ...
Colburn, N.H. [Hrsg.]
Metallothionein overexpression protects from MNNG-induced alkylation death. (1988)
Kaina, B., Lohrer, H., Karin, M., Herrlich, P.
NATO-Advanced Workshop 'DNA Repair Mechanisms' Fontevraud, F, October 2-7, 1988
Progesterone induction of metallothionein-II§A gene expression. (1988)
Slater, E.P., Cato, A.C.B., Karin, M., Baxter, J.D., Beato, M.
Molecular Endocrinology, 2(1988) S.485-91
Buescher, M., Rahmsdorf, H.J., Litfin, M., Karin, M., Herrlich, P.
Oncogene, 3(1988) S.301-11
Regulation of gene expression by posttranslational modification of transcription factors. (1988)
Kleinkauf, H. [Hrsg.]
DNA damage inducible responses in mammalian cells. (1987)
Herrlich, P., Imagawa, M., Angel, P., Buescher, M., Karin, M., Rahmsdorf, H.J., ...
British Association for Cancer Research Annual General Meeting, Univ.of Newcastle upon Tyne, GB, April 5-8, 1987
Post-translational modulation of enhancer factors by phorbol esters and UV irradiation. (1987)
Herrlich, P., Angel, P., Buescher, M., Rahmsdorf, H.J., Stein, B., Imagawa, M., ...
EMBO-Meeting 'Oncogenesis and Growth Control', Heidelberg, April 26-30, 1987
TPA induction of the human collagenase gene is mediated by an 8bp inducible enhancer element. (1987)
Stein, B., Angel, P., Rahmsdorf, H.J., Imagawa, M., Chiu, R., Karin, M., ...
Tagung der Gesellschaft fuer Genetik, Martinsried, 28.-30.Mai 1987
Angel, P., Imagawa, M., Chiu, R., Stein, B., Imbra, R.J., Rahmsdorf, H.J., ...
Cell, 49(1987) S.729-39
Preformed regulatory proteins as targets of carcinogen action. (1987)
Herrlich, P., Stein, B., Rahmsdorf, H.J., Buescher, M., Schoenthal, A., Angel, P., ...
Japanese-German Workshop on 'Molecular Aspects of Cacinogenesis', Essen, October 1-3, 1987
Hormonal and environmental control of metallothionein gene expression. (1987)
Karin, M., Imagawa, M., Imbra, R.J., Chiu, R., Heguy, A., Haslinger, A., ...
Granner, D. et al. [Hrsg.]
Herrlich, P., Imagawa, M., Maher, V., Sato, K., Mc Cormick, J.J., Angel, P., ...
Accomplishments in Oncology, 2(1987) S.95-105
The human metallothionein II§A promoter can be induced by progestins in mammary cell lines. (1985)
Cato, A.C.B., Krauter, P., Karin, M., Beato, M.
2nd Internat.Meeting on Metallothionein, Zuerich, CH, August 21-24, 1985
The metallothionein gene reveals a general stress sensing mechanism. (1985)
Herrlich, P., Karin, M., Rahmsdorf, H.J., Angel, P., Cato, A.C.B.
11th EMBO Annual Symp. 'Growth Factors, Receptors and Oncogenes', Heidelberg, September 16-19, 1985
Karin, M, Eberhardt, N L, Mellon, S H, Malich, N, Richards, R I, Slater, E P, ...
Expression of the rat growth hormone (rGH) gene in the pituitary and in cultured pituitary tumor cells is regulated by glucocorticoid hormones. After co-transfer of cloned DNA containing the rGH gene...
A method for isolation of intact, translationally active ribonucleic acid (1983)
Cathala, G, Savouret, J F, Mendez, B, West, B L, Karin, M, Martial, Joseph, ...
A method for isolation of large, translationally active RNA species is presented. The procedure involves homogenization of cells or tissues in 5 M guanidine monothiocyanate followed by direct...
Yoshioka, K, Deng, T, Cavigelli, M, Karin, M
Induction of phase 2 detoxification enzymes by phenolic antioxidants can account for prevention of tumor initiation but cannot explain why these compounds inhibit tumor promotion. Phase 2 genes are...
Westwick, J K, Cox, A D, Der, C J, Cobb, M H, Hibi, M, Karin, M, ...
c-Jun transcriptional activity is augmented by expression of oncogenic Ras and Raf proteins. This study demonstrates a direct correlation between Ras transforming activity and c-Jun activation,...
c-Jun is a typical member of the bZIP (basic zipper) family of dimeric transcriptional activators. These proteins contain a basic region responsible for DNA sequence recognition and a leucine zipper...
Kaina, B, Lohrer, H, Karin, M, Herrlich, P
Experiments were designed to detect survival advantages that cells gain by overexpressing metallothionein (MT). Chinese hamster ovary K1-2 cells and an x-ray-sensitive derivative were transfected...
DiDonato, J A, Mercurio, F, Karin, M
NF-kappa B is an important activator of immune and inflammatory response genes. NF-kappa B is sequestered in the cytoplasm of nonstimulated cells through interaction with the I kappa B inhibitors....
Caelles, C, Hennemann, H, Karin, M
GHF-1 is a member of the POU family of homeodomain proteins. It is a cell-type-specific transcription factor responsible for determination and expansion of growth hormone (GH)- and...
Claret, F X, Antakly, T, Karin, M, Saatcioglu, F
Thyroid hormone (T3) receptors (T3Rs) are ligand-modulated transcription factors that bind to thyroid hormone response elements (T3REs) and mediate either positive or negative transcriptional...
DiDonato, J, Mercurio, F, Rosette, C, Wu-Li, J, Suyang, H, Ghosh, S, ...
Extracellular stimuli that activate the transcription factor NF-kappaB cause rapid phosphorylation of the IkappaBalpha inhibitor, which retains NF-kappaB in the cytoplasm of nonstimulated cells....
The Ras-JNK pathway is involved in shear-induced gene expression.
Li, Y S, Shyy, J Y, Li, S, Lee, J, Su, B, Karin, M, ...
Hemodynamic forces play a key role in inducing atherosclerosis-implicated gene expression in vascular endothelial cells. To elucidate the signal transduction pathway leading to such gene expression,...
Isolation of an AP-1 repressor by a novel method for detecting protein-protein interactions.
Aronheim, A, Zandi, E, Hennemann, H, Elledge, S J, Karin, M
Transcription factor AP-1 transduces environmental signals to the transcriptional machinery. To ensure a quick response yet maintain tight control over AP-1 target genes, AP-1 activity is likely to...
Saatcioglu, F, Lopez, G, West, B L, Zandi, E, Feng, W, Lu, H, ...
A short C-terminal sequence that is deleted in the v-ErbA oncoprotein and conserved in members of the nuclear receptor superfamily is required for normal biological function of its normal cellular...
Wu, Z, Wu, J, Jacinto, E, Karin, M
At least three mitogen-activated protein kinase (MAPK) cascades were identified in mammals, each consisting of a well-defined three-kinase module composed of a MAPK, a MAPK kinase (MAPKK), and a...
Cytosine methylation does not affect binding of transcription factor Sp1.
Harrington, M A, Jones, P A, Imagawa, M, Karin, M
DNA methylation may be a component of a multilevel control mechanism that regulates eukaryotic gene expression. We used synthetic oligonucleotides to investigate the effect of cytosine methylation on...
Structure and chromosomal localization of the functional intronless human JUN protooncogene.
Hattori, K, Angel, P, Le Beau, M M, Karin, M
The JUN protooncogene encodes a protein that is functionally and biochemically identical to the transcription factor AP-1 (activator protein 1). To understand the structure and regulation of this...
Trautwein, C, Karin, M, Hunter, T, Chojkier, M
LAP (NF-IL6 or C/EBP beta), is a liver transcriptional activator protein that confers liver-specific gene expression. Because LAP has a characteristic phosphoacceptor sequence for cAMP-dependent...
Human metallothionein genes: molecular cloning and sequence analysis of the mRNA.
From a cDNA clone bank prepared from cadmium-treated HeLa cells, we isolated clones representing mRNAs whose concentration is increased after cadmium induction. Several metallothionein cDNA clones...
Primary structure and transcription of an amplified genetic locus: the CUP1 locus of yeast.
Karin, M, Najarian, R, Haslinger, A, Valenzuela, P, Welch, J, Fogel, S
Copper resistance in yeast is controlled by the CUP1 locus. The level of resistance is proportional to the copy number of this locus, which can be found in up to 15 tandemly iterated copies. To...
BCL3 encodes a nuclear protein which can alter the subcellular location of NF-kappa B proteins.
Zhang, Q, Didonato, J A, Karin, M, McKeithan, T W
BCL3 is a candidate proto-oncogene involved in the recurring translocation t(14;19) found in some patients with chronic lymphocytic leukemia. BCL3 protein acts as an I kappa B in that it can...
Engelberg, D, Zandi, E, Parker, C S, Karin, M
Yeast strains in which the Ras-cyclic AMP (cAMP) pathway is constitutively active are sensitive to heat shock, whereas mutants in which the activity of this pathway is low are hyperresistant to heat...
Saatcioglu, F, Bartunek, P, Deng, T, Zenke, M, Karin, M
The thyroid hormone (T3) receptor type alpha, the c-ErbA alpha proto-oncoprotein, stimulates transcription of T3-dependent promoters, interferes with AP-1 activity, and induces erythroid...
Rapid and preferential activation of the c-jun gene during the mammalian UV response.
Devary, Y, Gottlieb, R A, Lau, L F, Karin, M
Exposure of mammalian cells to DNA-damaging agents leads to activation of a genetic response known as the UV response. Because several previously identified UV-inducible genes contain AP-1 binding...
Trejo, J, Chambard, J C, Karin, M, Brown, J H
Activation of either muscarinic cholinergic or thrombin receptors increases phosphoinositide turnover, Ca2+ mobilization, and redistribution of protein kinase C and induces rapid transient increases...
A single amino acid change in CUP2 alters its mode of DNA binding.
Buchman, C, Skroch, P, Dixon, W, Tullius, T D, Karin, M
CUP2 is a copper-dependent transcriptional activator of the yeast CUP1 metallothionein gene. In the presence of Cu+ and Ag+) ions its DNA-binding domain is thought to fold as a cysteine-coordinated...
Regulation of collagenase gene expression by okadaic acid, an inhibitor of protein phosphatases.
Kim, S J, Lafyatis, R, Kim, K Y, Angel, P, Fujiki, H, Karin, M, ...
Human collagenase gene expression is regulated transcriptionally and is inducible by various mitogens in many cell types. To investigate the molecular mechanisms of this response, we examined the...
Alani, R, Brown, P, Binétruy, B, Dosaka, H, Rosenberg, R K, Angel, P, ...
The nuclear phosphoprotein c-Jun, encoded by the proto-oncogene c-jun, is a major component of the AP-1 complex. A potent transcriptional regulator, c-jun is also able to transform normal rat embryo...
Autoinduction of transforming growth factor beta 1 is mediated by the AP-1 complex.
Kim, S J, Angel, P, Lafyatis, R, Hattori, K, Kim, K Y, Sporn, M B, ...
The multifunctional actions of transforming growth factor beta 1 (TGF-beta 1) indicate that it has a pivotal control function in many physiological and pathological processes. An important property...
Buchman, C, Skroch, P, Welch, J, Fogel, S, Karin, M
CUP2 is a regulatory gene controlling expression of CUP1, which encodes the Cu-binding yeast metallothionein. CUP2, which is identical to the ACE1 gene, encodes a Cu-regulated DNA-binding protein....
Smeal, T, Binetruy, B, Mercola, D, Grover-Bardwick, A, Heidecker, G, Rapp, U R, ...
In resting cells, c-Jun is phosphorylated on five sites. Three of these sites reside next to its DNA binding domain and negatively regulate DNA binding. In response to expression of oncogenic Ha-Ras,...
Metal-responsive elements act as positive modulators of human metallothionein-IIA enhancer activity.
Karin, M, Haslinger, A, Heguy, A, Dietlin, T, Cooke, T
The human metallothionein IIA (hMT-IIA) gene contains two enhancer elements whose activity is induced by heavy-metal ions such as Cd2+. To determine the nature of the relationship between the...
Metallothionein gene expression is regulated by serum factors and activators of protein kinase C.
The exact physiological role of metallothionein (MT) is not clear. It has been suggested that these low-molecular-weight, highly inducible, heavy-metal-binding proteins serve in the regulation of...
Interleukin 1 regulates human metallothionein gene expression.
Karin, M, Imbra, R J, Heguy, A, Wong, G
Incubation of cultured human cells with interleukin 1 leads to increased expression of the human metallothionein-IIA gene. Recently, metallothionein has been shown to be an efficient free radical...
Structure and tissue-specific expression of the human metallothionein IB gene.
Heguy, A, West, A, Richards, R I, Karin, M
The human metallothionein (MT) IB gene (hMT-IB) is located in a region of human DNA containing at least four tandemly arranged MT genes. As deduced from its sequence, hMT-IB is likely to encode a...
Slater, E P, Rabenau, O, Karin, M, Baxter, J D, Beato, M
In this study DNA-binding and gene transfer experiments were performed to examine a potential glucocorticoid regulatory element (GRE) in the human growth hormone gene. As assayed by nitrocellulose...
Industrial yeasts display tandem gene iteration at the CUP1 region.
Welch, J W, Fogel, S, Cathala, G, Karin, M
The gene copy number at the CUP1 locus and the resistance level to external copper was directly correlated in five wild-type commercial Saccharomyces strains. An increased copy number of the CUP1...
Upstream promoter element of the human metallothionein-IIA gene can act like an enhancer element.
Initiation of transcription by RNA polymerase II in eukaryotes is strongly increased by cis-acting genetic elements, known as activators or enhancers. Enhancers, first detected in simian virus 40...
Human metallothionein genes are clustered on chromosome 16.
Karin, M, Eddy, R L, Henry, W M, Haley, L L, Byers, M G, Shows, T B
The metallothioneins are a family of heavy-metal binding proteins of low molecular weight. They function in the regulation of trace metal metabolism and in the protection against toxic heavy metal...
Karin, M, Cathala, G, Nguyen-Huu, M C
A human metallothionein (MT) gene was inserted into a bovine papillomavirus (BPV) vector. The chimeric vector (pMTII-BPV) transforms rodent fibroblasts to a cadmium-resistant phenotype. The...
Induction of c-fos expression through JNK-mediated TCF/Elk-1 phosphorylation.
Cavigelli, M, Dolfi, F, Claret, F X, Karin, M
Growth factors induce c-fos transcription by stimulating phosphorylation of transcription factor TCF/Elk-1, which binds to the serum response element (SRE). Under such conditions Elk-1 could be...
Protein phosphorylation is commonly used to modulate transcription factor activity. However, all existing genetic evidence for stimulation of transcription factor activity by phosphorylation rests on...
Helmberg, A, Auphan, N, Caelles, C, Karin, M
Induction of apoptosis in lymphocytes, which may account for the therapeutic effects of glucocorticoids in various diseases including leukemia, depends on the glucocorticoid receptor. However, the...
The CUP2 gene product regulates the expression of the CUP1 gene, coding for yeast metallothionein.
Welch, J, Fogel, S, Buchman, C, Karin, M
The yeast CUP1 gene codes for a copper-binding protein similar to metallothionein. Copper sensitive cup1s strains contain a single copy of the CUP1 locus. Resistant strains (CUP1r) carry 12 or more...
Serfling, E, Barthelmäs, R, Pfeuffer, I, Schenk, B, Zarius, S, Swoboda, R, ...
The immediate upstream region of the mouse interleukin 2 (Il-2) gene harbors a strong transcriptional enhancer. This enhancer contains most, if not all of the sequence elements necessary for the T...
Transcription factors AP-3 and AP-2 interact with the SV40 enhancer in a mutually exclusive manner.
The 'core' sequence is critical for efficient transcriptional activity of the SV40 enhancer. Moreover, the core was shown to be involved in a signal transduction pathway elicited by treatment of...
Metallothionein messenger RNA regulation in the mottled mouse and Menkes kinky hair syndrome.
Packman, S, Palmiter, R D, Karin, M, O'Toole, C
Menkes kinky hair syndrome is an X-linked neurodegenerative disorder, causing tissue-specific increases in copper and metallothionein content. A mouse model is provided by hemizygotes for mutant...
The tumor promoter arsenite stimulates AP-1 activity by inhibiting a JNK phosphatase.
Cavigelli, M, Li, W W, Lin, A, Su, B, Yoshioka, K, Karin, M
Trivalent arsenic (As3+) is highly carcinogenic, but devoid of known mutagenic activity. Therefore, it is likely to act as a tumor promoter. To understand the molecular basis for the tumor-promoting...
Haugen, T H, Turek, L P, Mercurio, F M, Cripe, T P, Olson, B J, Anderson, R D, ...
The sequence-specific trans-activator protein of bovine papillomavirus (BPV)-1, E2, strongly increases transcription at promoters containing papillomaviral ACCG(N)4CGGT (E2P) cis motifs, but can also...
Haugen, T H, Cripe, T P, Ginder, G D, Karin, M, Turek, L P
The approximately 1000 nucleotide long upstream regulatory region (URR) of bovine papilloma virus-1 (BPV-1) contains a cis element which responds to trans-activation by a diffusible factor encoded in...
Lefevre, C, Imagawa, M, Dana, S, Grindlay, J, Bodner, M, Karin, M
The molecular basis for the pituitary-specific expression of the human growth hormone (hGH) gene was investigated, by gene transfer and protein footprinting experiments. Plasmid constructs in which...
Dinter, H, Chiu, R, Imagawa, M, Karin, M, Jones, K A
The transition from persistent to lytic infection by the human immunodeficiency virus, HIV, is marked by a burst of viral replication and gene expression that occurs when infected cells are...
Theill, L E, Hattori, K, Lazzaro, D, Castrillo, J L, Karin, M
The POU domain protein GHF-1 has a critical role in generation, proliferation and phenotypic expression of three pituitary cell types. GHF-1 functions in part by binding to and transactivating the...
Werlen, G, Jacinto, E, Xia, Y, Karin, M
Costimulation of the T cell receptor (TCR) and CD28 is required for optimal interleukin-2 (IL-2) induction. These signals, which can be replaced by the pharmacological agents phorbol ester (PMA) and...
Minden, A, Lin, A, Smeal, T, Dérijard, B, Cobb, M, Davis, R, ...
c-Jun transcriptional activity is stimulated by phosphorylation at two N-terminal sites: Ser-63 and -73. Phosphorylation of these sites is enhanced in response to a variety of extracellular stimuli,...
Protein phosphatase 2A potentiates activity of promoters containing AP-1-binding elements.
Alberts, A S, Deng, T, Lin, A, Meinkoth, J L, Schönthal, A, Mumby, M C, ...
The involvement of serine/threonine protein phosphatases in signaling pathways which modulate the activity of the transcription factor AP-1 was examined. Purified protein phosphatase types 1 (PP1)...
The human metallothionein gene family: structure and expression.
Metallothioneins (MTs) are encoded by a multigene family in man. We have isolated those genes and analyzed the structure of some of them. The MT-II variant is encoded by a single functional gene:...
Yoshioka, K, Deng, T, Cavigelli, M, Karin, M
Induction of phase 2 detoxification enzymes by phenolic antioxidants can account for prevention of tumor initiation but cannot explain why these compounds inhibit tumor promotion. Phase 2 genes are...
Westwick, J K, Cox, A D, Der, C J, Cobb, M H, Hibi, M, Karin, M, ...
c-Jun transcriptional activity is augmented by expression of oncogenic Ras and Raf proteins. This study demonstrates a direct correlation between Ras transforming activity and c-Jun activation,...
c-Jun is a typical member of the bZIP (basic zipper) family of dimeric transcriptional activators. These proteins contain a basic region responsible for DNA sequence recognition and a leucine zipper...
Kaina, B, Lohrer, H, Karin, M, Herrlich, P
Experiments were designed to detect survival advantages that cells gain by overexpressing metallothionein (MT). Chinese hamster ovary K1-2 cells and an x-ray-sensitive derivative were transfected...
DiDonato, J A, Mercurio, F, Karin, M
NF-kappa B is an important activator of immune and inflammatory response genes. NF-kappa B is sequestered in the cytoplasm of nonstimulated cells through interaction with the I kappa B inhibitors....
Caelles, C, Hennemann, H, Karin, M
GHF-1 is a member of the POU family of homeodomain proteins. It is a cell-type-specific transcription factor responsible for determination and expansion of growth hormone (GH)- and...
Claret, F X, Antakly, T, Karin, M, Saatcioglu, F
Thyroid hormone (T3) receptors (T3Rs) are ligand-modulated transcription factors that bind to thyroid hormone response elements (T3REs) and mediate either positive or negative transcriptional...
DiDonato, J, Mercurio, F, Rosette, C, Wu-Li, J, Suyang, H, Ghosh, S, ...
Extracellular stimuli that activate the transcription factor NF-kappaB cause rapid phosphorylation of the IkappaBalpha inhibitor, which retains NF-kappaB in the cytoplasm of nonstimulated cells....
The Ras-JNK pathway is involved in shear-induced gene expression.
Li, Y S, Shyy, J Y, Li, S, Lee, J, Su, B, Karin, M, ...
Hemodynamic forces play a key role in inducing atherosclerosis-implicated gene expression in vascular endothelial cells. To elucidate the signal transduction pathway leading to such gene expression,...
Isolation of an AP-1 repressor by a novel method for detecting protein-protein interactions.
Aronheim, A, Zandi, E, Hennemann, H, Elledge, S J, Karin, M
Transcription factor AP-1 transduces environmental signals to the transcriptional machinery. To ensure a quick response yet maintain tight control over AP-1 target genes, AP-1 activity is likely to...
Saatcioglu, F, Lopez, G, West, B L, Zandi, E, Feng, W, Lu, H, ...
A short C-terminal sequence that is deleted in the v-ErbA oncoprotein and conserved in members of the nuclear receptor superfamily is required for normal biological function of its normal cellular...
Wu, Z, Wu, J, Jacinto, E, Karin, M
At least three mitogen-activated protein kinase (MAPK) cascades were identified in mammals, each consisting of a well-defined three-kinase module composed of a MAPK, a MAPK kinase (MAPKK), and a...
Cytosine methylation does not affect binding of transcription factor Sp1.
Harrington, M A, Jones, P A, Imagawa, M, Karin, M
DNA methylation may be a component of a multilevel control mechanism that regulates eukaryotic gene expression. We used synthetic oligonucleotides to investigate the effect of cytosine methylation on...
Structure and chromosomal localization of the functional intronless human JUN protooncogene.
Hattori, K, Angel, P, Le Beau, M M, Karin, M
The JUN protooncogene encodes a protein that is functionally and biochemically identical to the transcription factor AP-1 (activator protein 1). To understand the structure and regulation of this...
Trautwein, C, Karin, M, Hunter, T, Chojkier, M
LAP (NF-IL6 or C/EBP beta), is a liver transcriptional activator protein that confers liver-specific gene expression. Because LAP has a characteristic phosphoacceptor sequence for cAMP-dependent...
Human metallothionein genes: molecular cloning and sequence analysis of the mRNA.
From a cDNA clone bank prepared from cadmium-treated HeLa cells, we isolated clones representing mRNAs whose concentration is increased after cadmium induction. Several metallothionein cDNA clones...
Primary structure and transcription of an amplified genetic locus: the CUP1 locus of yeast.
Karin, M, Najarian, R, Haslinger, A, Valenzuela, P, Welch, J, Fogel, S
Copper resistance in yeast is controlled by the CUP1 locus. The level of resistance is proportional to the copy number of this locus, which can be found in up to 15 tandemly iterated copies. To...
BCL3 encodes a nuclear protein which can alter the subcellular location of NF-kappa B proteins.
Zhang, Q, Didonato, J A, Karin, M, McKeithan, T W
BCL3 is a candidate proto-oncogene involved in the recurring translocation t(14;19) found in some patients with chronic lymphocytic leukemia. BCL3 protein acts as an I kappa B in that it can...
Engelberg, D, Zandi, E, Parker, C S, Karin, M
Yeast strains in which the Ras-cyclic AMP (cAMP) pathway is constitutively active are sensitive to heat shock, whereas mutants in which the activity of this pathway is low are hyperresistant to heat...
Minden, A, Lin, A, Smeal, T, Dérijard, B, Cobb, M, Davis, R, ...
c-Jun transcriptional activity is stimulated by phosphorylation at two N-terminal sites: Ser-63 and -73. Phosphorylation of these sites is enhanced in response to a variety of extracellular stimuli,...
Protein phosphatase 2A potentiates activity of promoters containing AP-1-binding elements.
Alberts, A S, Deng, T, Lin, A, Meinkoth, J L, Schönthal, A, Mumby, M C, ...
The involvement of serine/threonine protein phosphatases in signaling pathways which modulate the activity of the transcription factor AP-1 was examined. Purified protein phosphatase types 1 (PP1)...
Saatcioglu, F, Bartunek, P, Deng, T, Zenke, M, Karin, M
The thyroid hormone (T3) receptor type alpha, the c-ErbA alpha proto-oncoprotein, stimulates transcription of T3-dependent promoters, interferes with AP-1 activity, and induces erythroid...
Rapid and preferential activation of the c-jun gene during the mammalian UV response.
Devary, Y, Gottlieb, R A, Lau, L F, Karin, M
Exposure of mammalian cells to DNA-damaging agents leads to activation of a genetic response known as the UV response. Because several previously identified UV-inducible genes contain AP-1 binding...
Trejo, J, Chambard, J C, Karin, M, Brown, J H
Activation of either muscarinic cholinergic or thrombin receptors increases phosphoinositide turnover, Ca2+ mobilization, and redistribution of protein kinase C and induces rapid transient increases...
A single amino acid change in CUP2 alters its mode of DNA binding.
Buchman, C, Skroch, P, Dixon, W, Tullius, T D, Karin, M
CUP2 is a copper-dependent transcriptional activator of the yeast CUP1 metallothionein gene. In the presence of Cu+ and Ag+) ions its DNA-binding domain is thought to fold as a cysteine-coordinated...
Regulation of collagenase gene expression by okadaic acid, an inhibitor of protein phosphatases.
Kim, S J, Lafyatis, R, Kim, K Y, Angel, P, Fujiki, H, Karin, M, ...
Human collagenase gene expression is regulated transcriptionally and is inducible by various mitogens in many cell types. To investigate the molecular mechanisms of this response, we examined the...
Alani, R, Brown, P, Binétruy, B, Dosaka, H, Rosenberg, R K, Angel, P, ...
The nuclear phosphoprotein c-Jun, encoded by the proto-oncogene c-jun, is a major component of the AP-1 complex. A potent transcriptional regulator, c-jun is also able to transform normal rat embryo...
Autoinduction of transforming growth factor beta 1 is mediated by the AP-1 complex.
Kim, S J, Angel, P, Lafyatis, R, Hattori, K, Kim, K Y, Sporn, M B, ...
The multifunctional actions of transforming growth factor beta 1 (TGF-beta 1) indicate that it has a pivotal control function in many physiological and pathological processes. An important property...
Buchman, C, Skroch, P, Welch, J, Fogel, S, Karin, M
CUP2 is a regulatory gene controlling expression of CUP1, which encodes the Cu-binding yeast metallothionein. CUP2, which is identical to the ACE1 gene, encodes a Cu-regulated DNA-binding protein....
Smeal, T, Binetruy, B, Mercola, D, Grover-Bardwick, A, Heidecker, G, Rapp, U R, ...
In resting cells, c-Jun is phosphorylated on five sites. Three of these sites reside next to its DNA binding domain and negatively regulate DNA binding. In response to expression of oncogenic Ha-Ras,...
Metal-responsive elements act as positive modulators of human metallothionein-IIA enhancer activity.
Karin, M, Haslinger, A, Heguy, A, Dietlin, T, Cooke, T
The human metallothionein IIA (hMT-IIA) gene contains two enhancer elements whose activity is induced by heavy-metal ions such as Cd2+. To determine the nature of the relationship between the...
Metallothionein gene expression is regulated by serum factors and activators of protein kinase C.
The exact physiological role of metallothionein (MT) is not clear. It has been suggested that these low-molecular-weight, highly inducible, heavy-metal-binding proteins serve in the regulation of...
Interleukin 1 regulates human metallothionein gene expression.
Karin, M, Imbra, R J, Heguy, A, Wong, G
Incubation of cultured human cells with interleukin 1 leads to increased expression of the human metallothionein-IIA gene. Recently, metallothionein has been shown to be an efficient free radical...
Structure and tissue-specific expression of the human metallothionein IB gene.
Heguy, A, West, A, Richards, R I, Karin, M
The human metallothionein (MT) IB gene (hMT-IB) is located in a region of human DNA containing at least four tandemly arranged MT genes. As deduced from its sequence, hMT-IB is likely to encode a...
Slater, E P, Rabenau, O, Karin, M, Baxter, J D, Beato, M
In this study DNA-binding and gene transfer experiments were performed to examine a potential glucocorticoid regulatory element (GRE) in the human growth hormone gene. As assayed by nitrocellulose...
Industrial yeasts display tandem gene iteration at the CUP1 region.
Welch, J W, Fogel, S, Cathala, G, Karin, M
The gene copy number at the CUP1 locus and the resistance level to external copper was directly correlated in five wild-type commercial Saccharomyces strains. An increased copy number of the CUP1...
Upstream promoter element of the human metallothionein-IIA gene can act like an enhancer element.
Initiation of transcription by RNA polymerase II in eukaryotes is strongly increased by cis-acting genetic elements, known as activators or enhancers. Enhancers, first detected in simian virus 40...
Human metallothionein genes are clustered on chromosome 16.
Karin, M, Eddy, R L, Henry, W M, Haley, L L, Byers, M G, Shows, T B
The metallothioneins are a family of heavy-metal binding proteins of low molecular weight. They function in the regulation of trace metal metabolism and in the protection against toxic heavy metal...
Karin, M, Cathala, G, Nguyen-Huu, M C
A human metallothionein (MT) gene was inserted into a bovine papillomavirus (BPV) vector. The chimeric vector (pMTII-BPV) transforms rodent fibroblasts to a cadmium-resistant phenotype. The...
Induction of c-fos expression through JNK-mediated TCF/Elk-1 phosphorylation.
Cavigelli, M, Dolfi, F, Claret, F X, Karin, M
Growth factors induce c-fos transcription by stimulating phosphorylation of transcription factor TCF/Elk-1, which binds to the serum response element (SRE). Under such conditions Elk-1 could be...
Protein phosphorylation is commonly used to modulate transcription factor activity. However, all existing genetic evidence for stimulation of transcription factor activity by phosphorylation rests on...
Helmberg, A, Auphan, N, Caelles, C, Karin, M
Induction of apoptosis in lymphocytes, which may account for the therapeutic effects of glucocorticoids in various diseases including leukemia, depends on the glucocorticoid receptor. However, the...
The CUP2 gene product regulates the expression of the CUP1 gene, coding for yeast metallothionein.
Welch, J, Fogel, S, Buchman, C, Karin, M
The yeast CUP1 gene codes for a copper-binding protein similar to metallothionein. Copper sensitive cup1s strains contain a single copy of the CUP1 locus. Resistant strains (CUP1r) carry 12 or more...
Serfling, E, Barthelmäs, R, Pfeuffer, I, Schenk, B, Zarius, S, Swoboda, R, ...
The immediate upstream region of the mouse interleukin 2 (Il-2) gene harbors a strong transcriptional enhancer. This enhancer contains most, if not all of the sequence elements necessary for the T...
Transcription factors AP-3 and AP-2 interact with the SV40 enhancer in a mutually exclusive manner.
The 'core' sequence is critical for efficient transcriptional activity of the SV40 enhancer. Moreover, the core was shown to be involved in a signal transduction pathway elicited by treatment of...
Metallothionein messenger RNA regulation in the mottled mouse and Menkes kinky hair syndrome.
Packman, S, Palmiter, R D, Karin, M, O'Toole, C
Menkes kinky hair syndrome is an X-linked neurodegenerative disorder, causing tissue-specific increases in copper and metallothionein content. A mouse model is provided by hemizygotes for mutant...
The tumor promoter arsenite stimulates AP-1 activity by inhibiting a JNK phosphatase.
Cavigelli, M, Li, W W, Lin, A, Su, B, Yoshioka, K, Karin, M
Trivalent arsenic (As3+) is highly carcinogenic, but devoid of known mutagenic activity. Therefore, it is likely to act as a tumor promoter. To understand the molecular basis for the tumor-promoting...
Haugen, T H, Turek, L P, Mercurio, F M, Cripe, T P, Olson, B J, Anderson, R D, ...
The sequence-specific trans-activator protein of bovine papillomavirus (BPV)-1, E2, strongly increases transcription at promoters containing papillomaviral ACCG(N)4CGGT (E2P) cis motifs, but can also...
Haugen, T H, Cripe, T P, Ginder, G D, Karin, M, Turek, L P
The approximately 1000 nucleotide long upstream regulatory region (URR) of bovine papilloma virus-1 (BPV-1) contains a cis element which responds to trans-activation by a diffusible factor encoded in...
Lefevre, C, Imagawa, M, Dana, S, Grindlay, J, Bodner, M, Karin, M
The molecular basis for the pituitary-specific expression of the human growth hormone (hGH) gene was investigated, by gene transfer and protein footprinting experiments. Plasmid constructs in which...
Dinter, H, Chiu, R, Imagawa, M, Karin, M, Jones, K A
The transition from persistent to lytic infection by the human immunodeficiency virus, HIV, is marked by a burst of viral replication and gene expression that occurs when infected cells are...
Theill, L E, Hattori, K, Lazzaro, D, Castrillo, J L, Karin, M
The POU domain protein GHF-1 has a critical role in generation, proliferation and phenotypic expression of three pituitary cell types. GHF-1 functions in part by binding to and transactivating the...
Werlen, G, Jacinto, E, Xia, Y, Karin, M
Costimulation of the T cell receptor (TCR) and CD28 is required for optimal interleukin-2 (IL-2) induction. These signals, which can be replaced by the pharmacological agents phorbol ester (PMA) and...
The human metallothionein gene family: structure and expression.
Metallothioneins (MTs) are encoded by a multigene family in man. We have isolated those genes and analyzed the structure of some of them. The MT-II variant is encoded by a single functional gene:...
IKKß as a target for treatment of inflammation induced bone loss
The transcription factor nuclear factor (NF)-κB is well recognised as a pivotal player in osteoclastogenesis and inflammation induced bone loss. Here, the authors discuss their recent results,...