Research Topics
Genomes and Genes
| Michael KarinSummaryAffiliation: University of California Country: USA Publications
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Publications
The lymphotoxin-beta receptor induces different patterns of gene expression via two NF-kappaB pathwaysEmmanuel Dejardin
Division of Cellular Immunology, La Jolla Institute for Allergy and Immunology, San Diego, CA 92121, USA
Immunity 17:525-35. 2002..In contrast, IKKalpha controls the induction by LTbetaR ligation of chemokines and cytokines involved in lymphoid organogenesis, including SLC, BLC, ELC, SDF1, and BAFF...
Implications of anti-cytokine therapy in colorectal cancer and autoimmune diseasesKepeng Wang
Correspondence to Dr Michael Karin, Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology and Pathology, School of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093 0723, USA
Ann Rheum Dis 72:ii100-ii103. 2013..These findings suggest that such cytokines or the cells that produce them may provide new therapeutic or preventive targets in forms of colorectal cancer that are linked to inflammation...- Innate immunity gone awry: linking microbial infections to chronic inflammation and cancerMichael Karin
Laboratory of Gene Expression and Signal Transduction, Department of Pharmacology, UCSD School of Medicine, 9500 Gilman Drive, La Jolla, CA 92093, USA
Cell 124:823-35. 2006.... - The IkappaB kinase - a bridge between inflammation and cancerMichael Karin
Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, Cancer Center, School of Medicine, University of California, San Diego, 9500 Gilman Drive, MC 0723, La Jolla, CA 92093 0723, USA
Cell Res 18:334-42. 2008..Unlike cancer cells, inflammatory cells retain a normal and stable genome and therefore are unlikely to become genetically resistant to therapeutic intervention... - TNFR signaling: ubiquitin-conjugated TRAFfic signals control stop-and-go for MAPK signaling complexesMichael Karin
Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, School of Medicine, University of California San Diego, La Jolla, CA 92093 0723, USA
Immunol Rev 228:225-40. 2009..This arrangement may be important for ensuring the proper delivery of NF-kappaB-dependent survival signals and conversion of JNK-promoted death signals to proliferative ones... - The IKK NF-kappa B system: a treasure trove for drug developmentMichael Karin
Laboratory of Gene Regulation and Signal Transduction Department of Pharmacology, School of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, California 92093-0636, USA
Nat Rev Drug Discov 3:17-26. 2004 - From JNK to pay dirt: jun kinases, their biochemistry, physiology and clinical importanceMichael Karin
Department of Pharmacology, School of Medicine, University of California, San Diego, California 92093 0723, USA
IUBMB Life 57:283-95. 2005..Importantly, the JNKs have become prime targets for drug development in several important clinical areas, including: inflammation, diabetes, and cancer... - Is NF-kappaB2/p100 a direct activator of programmed cell death?Hans Hacker
Department of Pharmacology, School of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA
Cancer Cell 2:431-3. 2002..Further, it is suggested that loss of the proapoptotic function of NF-kappaB2/p100 is directly linked to its oncogenic activity in lymphomas... - NF-kappaB: linking inflammation and immunity to cancer development and progressionMichael Karin
Laboratory of Gene Regulation and Signal Transduction, University of California at San Diego School of Medicine, Department of Pharmacology, 9500 Gilman Drive, La Jolla, California 92093 0723, USA
Nat Rev Immunol 5:749-59. 2005.... 
Role for IKK2 in muscle: waste not, want notMichael Karin
Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, School of Medicine, University of California San Diego, La Jolla, California 92093, USA
J Clin Invest 116:2866-8. 2006....- Phosphorylation meets ubiquitination: the control of NF-[kappa]B activityM Karin
Department of Pharmacology, Laboratory of Gene Regulation and Signal Transduction University of California, San Diego, La Jolla, California 92093 0636, USA
Annu Rev Immunol 18:621-63. 2000.... - NF-kappaB at the crossroads of life and deathMichael Karin
Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093 0636, USA
Nat Immunol 3:221-7. 2002..However, NF-kappaB cannot function alone. A variety of mechanisms exist to modulate its activity and thereby affect the ultimate outcome of a cell's fate... - Mitogen activated protein kinases as targets for development of novel anti-inflammatory drugsM Karin
Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, School of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093 0723, USA
Ann Rheum Dis 63:ii62-ii64. 2004..This report focuses on the possible mechanisms through which such inhibitors may interfere with inflammation and discusses the pros and cons of targeting MAPKs in the treatment of chronic inflammatory disease... - Inflammation-activated protein kinases as targets for drug developmentMichael Karin
Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, University of California, San Diego School of Medicine, 9500 Gilman Drive, La Jolla, CA 92093 0723, USA
Proc Am Thorac Soc 2:386-90; discussion 394-5. 2005..This review focuses on the possible mechanisms through which such inhibitors may interfere with inflammation and some of the complications that may be associated with their use... - Nuclear factor-kappaB in cancer development and progressionMichael Karin
Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, University of California San Diego School of Medicine, 9500 Gilman Drive, La Jolla, California 92093, USA
Nature 441:431-6. 2006..NF-kappaB might also regulate tumour angiogenesis and invasiveness, and the signalling pathways that mediate its activation provide attractive targets for new chemopreventive and chemotherapeutic approaches... - AP-1--glucocorticoid receptor crosstalk taken to a higher levelM Karin
Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, UCSD School of Medicine, 9500 Gilman Drive, La Jolla, California 92093 0636, USA
J Endocrinol 169:447-51. 2001..This negative feedback loop is likely to be of great importance for maintenance of homeostasis and regulation of stress responses, including acute and chronic inflammation... - NF-kappaB in cancer: from innocent bystander to major culpritMichael Karin
Department of Pharmacology, School of Medicine, University of California San Diego, La Jolla 92093, USA
Nat Rev Cancer 2:301-10. 2002..NF-kappaB should therefore receive as much attention from cancer researchers as it has already from immunologists... - Different modes of ubiquitination of the adaptor TRAF3 selectively activate the expression of type I interferons and proinflammatory cytokinesPing Hui Tseng
Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology and Department of Pathology, School of Medicine, University of California San Diego, La Jolla, California, USA
Nat Immunol 11:70-5. 2010..Inhibition of degradative ubiquitination of TRAF3 prevented the expression of all proinflammatory cytokines without affecting the interferon response... - IKKbeta couples hepatocyte death to cytokine-driven compensatory proliferation that promotes chemical hepatocarcinogenesisShin Maeda
Laboratory of Gene Regulation and Signal Transduction, University of California, San Diego, 9500 Gilman Drive MC 0723, La Jolla, California 92093, USA
Cell 121:977-90. 2005..IKKbeta, therefore, orchestrates inflammatory crosstalk between hepatocytes and hematopoietic-derived cells that promotes chemical hepatocarcinogenesis... - Essential cytoplasmic translocation of a cytokine receptor-assembled signaling complexAtsushi Matsuzawa
Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, School of Medicine, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093 0723, USA
Science 321:663-8. 2008..This two-stage signaling mechanism may apply to other innate immune receptors, accounting for spatial and temporal separation of MAPK and IKK signaling... - Hepatocyte necrosis induced by oxidative stress and IL-1 alpha release mediate carcinogen-induced compensatory proliferation and liver tumorigenesisToshiharu Sakurai
Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, School of Medicine, University of California, San Diego, La Jolla, CA 92093, USA
Cancer Cell 14:156-65. 2008..IL-1 alpha release by necrotic hepatocytes is therefore an important mediator of liver tumorigenesis... - I{kappa}B kinase (IKK){beta}, but not IKK{alpha}, is a critical mediator of osteoclast survival and is required for inflammation-induced bone lossMaria Grazia Ruocco
Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, School of Medicine, University of California, San Diego, La Jolla, CA 92093, USA
J Exp Med 201:1677-87. 2005..IKKbeta also protects osteoclasts and their progenitors from tumor necrosis factor alpha-induced apoptosis, and its loss in hematopoietic cells prevents inflammation-induced bone loss... - Adenoma-linked barrier defects and microbial products drive IL-23/IL-17-mediated tumour growthSergei I Grivennikov
Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, School of Medicine, University of California, San Diego, La Jolla, California 92093 0723, USA
Nature 491:254-8. 2012..We propose that barrier deterioration induced by colorectal-cancer-initiating genetic lesions results in adenoma invasion by microbial products that trigger tumour-elicited inflammation, which in turn drives tumour growth... - Signaling pathways and genes that inhibit pathogen-induced macrophage apoptosis--CREB and NF-kappaB as key regulatorsJin Mo Park
Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, University of California San Diego, La Jolla, CA 92093, USA
Immunity 23:319-29. 2005..Here we describe key roles for transcription factor CREB, a target for p38 signaling, and the plasminogen activator 2 (PAI-2) gene, a target for CREB, in maintenance of macrophage survival... - Carcinoma-produced factors activate myeloid cells through TLR2 to stimulate metastasisSunhwa Kim
Department of Pharmacology and Cancer Center, School of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, California 92093 0723, USA
Nature 457:102-6. 2009..These results explain how advanced cancer cells usurp components of the host innate immune system, including bone-marrow-derived myeloid progenitors, to generate an inflammatory microenvironment hospitable for metastatic growth... - IL-6 and Stat3 are required for survival of intestinal epithelial cells and development of colitis-associated cancerSergei Grivennikov
Laboratory of Gene Regulation and Signal Transduction, UCSD School of Medicine, University of California San Diego, La Jolla, CA 92093 0723, USA
Cancer Cell 15:103-13. 2009..Thus, the NF-kappaB-IL-6-Stat3 cascade is an important regulator of the proliferation and survival of tumor-initiating IECs... - Nod2 mutation in Crohn's disease potentiates NF-kappaB activity and IL-1beta processingShin Maeda
Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, School of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093 0723, USA
Science 307:734-8. 2005..These effects are linked to increased susceptibility to bacterial-induced intestinal inflammation and identify NOD2 as a positive regulator of NF-kappaB activation and IL-1beta secretion... - Nonredundant and complementary functions of TRAF2 and TRAF3 in a ubiquitination cascade that activates NIK-dependent alternative NF-kappaB signalingSivakumar Vallabhapurapu
Laboratory of Gene Regulation and Signal Transduction, Departments of Pharmacology and Pathology, Cancer Center, University of California, San Diego, California 93093, USA
Nat Immunol 9:1364-70. 2008..Constitutive activation of this pathway causes perinatal lethality and lymphoid defects... - Design and characterization of a potent and selective dual ATP- and substrate-competitive subnanomolar bidentate c-Jun N-terminal kinase (JNK) inhibitorJohn L Stebbins
Infectious and Inflammatory Disease Center, Cancer Center, Sanford Burnham Medical Research Institute, La Jolla, California 92037, USA
J Med Chem 54:6206-14. 2011..Finally, compound 19 successfully inhibits JNK in a variety of cell-based experiments, as well as in vivo where it is shown to protect against Jo-2 induced liver damage and improve glucose tolerance in diabetic mice... - Dietary and genetic obesity promote liver inflammation and tumorigenesis by enhancing IL-6 and TNF expressionEek Joong Park
Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, School of Medicine, University of California, San Diego, La Jolla, CA 92093, USA
Cell 140:197-208. 2010..The chronic inflammatory response caused by obesity and enhanced production of IL-6 and TNF may also increase the risk of other cancers... - Loss of hepatic NF-kappa B activity enhances chemical hepatocarcinogenesis through sustained c-Jun N-terminal kinase 1 activationToshiharu Sakurai
Laboratory of Gene Regulation and Signal Transduction, School of Medicine, University of California at San Diego, 9500 Gilman Drive MC 0723, La Jolla, CA 92093 0723, USA
Proc Natl Acad Sci U S A 103:10544-51. 2006.... - IKKbeta is required for prevention of apoptosis mediated by cell-bound but not by circulating TNFalphaShin Maeda
Laboratory of Gene Regulation and Signal Transduction, University of California, San Diego, 9500 Gilman Drive, 92093, La Jolla, CA, USA
Immunity 19:725-37. 2003..Thus, the antiapoptotic function of IKKbeta, which is most critical in situations that involve cell-bound TNFalpha, is mediated partially through attenuation of JNK activity... - Convergence of Itch-induced ubiquitination with MEKK1-JNK signaling in Th2 tolerance and airway inflammationK Venuprasad
Division of Cell Biology, La Jolla Institute for Allergy and Immunology, San Diego, California 92121, USA
J Clin Invest 116:1117-26. 2006..This study suggests that MEKK1-JNK signaling regulates Itch E3 ligase-mediated tolerogenic process in Th2 cells. These findings have therapeutic implications for allergic diseases... - Hepatocyte IKKbeta/NF-kappaB inhibits tumor promotion and progression by preventing oxidative stress-driven STAT3 activationGuobin He
Laboratory of Gene Regulation and Signal Transduction, School of Medicine, University of California, San Diego, La Jolla, CA 92093, USA
Cancer Cell 17:286-97. 2010..Hepatocyte-specific STAT3 ablation prevented HCC development. The negative crosstalk between NF-kappaB and STAT3, which is also evident in human HCC, is a critical regulator of liver cancer development and progression... - Alternative and classical NF-kappa B signaling retain autoreactive B cells in the splenic marginal zone and result in lupus-like diseaseThomas Enzler
Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, School of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, California 92093, USA
Immunity 25:403-15. 2006..Thus, both classical and alternative NF-kappaB signaling are important for development of lupus-like disease associated with BAFF overproduction. The same mechanisms may be involved in the pathogenesis of human SLE... - Jun turnover is controlled through JNK-dependent phosphorylation of the E3 ligase ItchMin Gao
Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, School of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093 0723, USA
Science 306:271-5. 2004..This pathway modulates cytokine production by effector T cells... - Tobacco smoke promotes lung tumorigenesis by triggering IKKbeta- and JNK1-dependent inflammationHiroyuki Takahashi
Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, University of California, San Diego, School of Medicine, La Jolla, CA 92093 0723, USA
Cancer Cell 17:89-97. 2010..Tumor promotion is due to induction of inflammation that results in enhanced pneumocyte proliferation and is abrogated by IKKbeta ablation in myeloid cells or inactivation of JNK1... - IKKalpha limits macrophage NF-kappaB activation and contributes to the resolution of inflammationToby Lawrence
Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, University of California San Diego, 9500 Gilman Drive, California 92093, USA
Nature 434:1138-43. 2005..Inactivation of IKKalpha in mice enhances inflammation and bacterial clearance. Hence, the two IKK catalytic subunits have evolved opposing but complimentary roles needed for the intricate control of inflammation and innate immunity... - Constitutive intestinal NF-κB does not trigger destructive inflammation unless accompanied by MAPK activationMonica Guma
Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, School of Medicine, University of California, San Diego, La Jolla, CA 92093, USA
J Exp Med 208:1889-900. 2011..Inflammation is driven by massive TNF production, which requires additional activation of p38 and extracellular-signal-regulated kinase mitogen-activated protein kinases (MAPKs)... - Macrophage apoptosis by anthrax lethal factor through p38 MAP kinase inhibitionJin Mo Park
Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, School of Medicine, University of California, San Diego, La Jolla, CA 92093 0636, USA
Science 297:2048-51. 2002..This dismantling of the p38 MAPK module represents a strategy used by B. anthracis to paralyze host innate immunity... - Anthrolysin O and other gram-positive cytolysins are toll-like receptor 4 agonistsJin Mo Park
Laboratory of Gene Regulation and Signal Transduction, Dept of Pharmacology, School of Medicine, University of California, San Diego, 9500 Gilman Dr, La Jolla, CA 92093, USA
J Exp Med 200:1647-55. 2004..We also provide genetic evidence that ALO is required for induction of macrophage apoptosis in response to infection with live B. anthracis and that other CDC family members share the ability to activate TLR4... - Targeted deletion of hepatocyte Ikkbeta confers growth advantagesKatherine S Koch
Hepatocyte Growth Control and Stem Cell Laboratory, School of Medicine, University of California at San Diego, 9500 Gilman Drive MC 0636, La Jolla, CA 92093 0636, USA
Biochem Biophys Res Commun 380:349-54. 2009..Increased HCC development in Ikkbeta(Delta hep) mice may also be caused by growth advantages of surviving Ikkbeta-deleted hepatocytes... - Inhibition of NF-kappaB in cancer cells converts inflammation- induced tumor growth mediated by TNFalpha to TRAIL-mediated tumor regressionJun-Li Luo
Laboratory of Gene Regulation and Signal Transduction, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA
Cancer Cell 6:297-305. 2004..The latter response is TNFalpha-independent, but depends on another member of the TNF superfamily, TRAIL, whose receptor is induced in NF-kappaB-deficient cancer cells... - Saturated fatty acids inhibit induction of insulin gene transcription by JNK-mediated phosphorylation of insulin-receptor substratesGiovanni Solinas
Laboratory of Gene Regulation and Signal Transduction, School of Medicine, University of California at San Diego, 9500 Gilman Drive, MC 0723, La Jolla, CA 92093 0723, USA
Proc Natl Acad Sci U S A 103:16454-9. 2006..This mechanism may account for the induction of central insulin resistance by free fatty acids... - Chronic lymphocytic leukemia of Emu-TCL1 transgenic mice undergoes rapid cell turnover that can be offset by extrinsic CD257 to accelerate disease progressionThomas Enzler
Moores Cancer Center, Department of Medicine, School of Medicine, University of California San Diego, La Jolla, CA, USA
Blood 114:4469-76. 2009.... - The human CYP1A1 gene is regulated in a developmental and tissue-specific fashion in transgenic miceAlema Galijatovic
Laboratory of Environmental Toxicology, Department of Pharmacology, University of California, San Diego, La Jolla 92093, USA
J Biol Chem 279:23969-76. 2004..Combined these results indicate that tissue-specific and developmental factors are controlling aryl hydrocarbon receptor-mediated induction of human CYP1A1... - IKK-beta links inflammation to obesity-induced insulin resistanceMelek C Arkan
Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, School of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, California 92093, USA
Nat Med 11:191-8. 2005..We suggest that inhibition of IKK-beta, especially in myeloid cells, may be used to treat insulin resistance... - Gender disparity in liver cancer due to sex differences in MyD88-dependent IL-6 productionWillscott E Naugler
Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology and Cancer Center, University of California, San Diego, CA 93093, USA
Science 317:121-4. 2007..We propose that estrogen-mediated inhibition of IL-6 production by KCs reduces liver cancer risk in females, and these findings may be used to prevent HCC in males... - Sestrin as a feedback inhibitor of TOR that prevents age-related pathologiesJun Hee Lee
Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, School of Medicine, University of California San Diego UCSD, La Jolla, CA 92093 0723, USA
Science 327:1223-8. 2010.... - Kinase MEKK1 is required for CD40-dependent activation of the kinases Jnk and p38, germinal center formation, B cell proliferation and antibody productionEwen Gallagher
Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, School of Medicine, University of California San Diego, La Jolla, California 92093 0723, USA
Nat Immunol 8:57-63. 2007..Our data emphasize that MEKK1 is an essential component of signaling cascades needed for thymus-dependent antigen-induced B cell proliferation and antibody production... - Dangerous liaisons: STAT3 and NF-kappaB collaboration and crosstalk in cancerSergei I Grivennikov
Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, School of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA, 92093, USA
Cytokine Growth Factor Rev 21:11-9. 2010..In addition to explaining the molecular pathogenesis of cancer, these interactions also offer opportunities for the design of new therapeutic interventions... - Maintenance of metabolic homeostasis by Sestrin2 and Sestrin3Jun Hee Lee
Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, University of California, San Diego, San Diego, CA 92093, USA
Cell Metab 16:311-21. 2012..These results demonstrate an important homeostatic function for the stress-inducible Sestrin protein family in the control of mammalian lipid and glucose metabolism... - The role of the Ah receptor and p38 in benzo[a]pyrene-7,8-dihydrodiol and benzo[a]pyrene-7,8-dihydrodiol-9,10-epoxide-induced apoptosisShujuan Chen
Laboratory of Environmental Toxicology, Department of Pharmacology, University of California, San Diego, La Jolla, California 92093 0636, USA
J Biol Chem 278:19526-33. 2003..These results confirm that the Ah receptor plays a critical role in B[a]P-7,8-dihydrodiol-induced apoptosis while p38 MAP kinase links the actions of an electrophilic metabolite like BPDE-2 to the regulation of programmed cell death... - IKKbeta links inflammation and tumorigenesis in a mouse model of colitis-associated cancerFlorian R Greten
Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, University of California, San Diego, 9500 Gilman Drive, La Jolla 92093, USA
Cell 118:285-96. 2004..In addition to suppressing apoptosis in advanced tumors, IKKbeta may link inflammation to cancer... - Activation of IKKalpha target genes depends on recognition of specific kappaB binding sites by RelB:p52 dimersGiuseppina Bonizzi
Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, School of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093 0636, USA
EMBO J 23:4202-10. 2004..This site links induction of organogenic chemokines and other important regulatory molecules to activation of the alternative pathway... - A NOD2-NALP1 complex mediates caspase-1-dependent IL-1beta secretion in response to Bacillus anthracis infection and muramyl dipeptideLi Chung Hsu
Departments of Pharmacology and Pathology, University of California at San Diego, La Jolla, CA 92093, USA
Proc Natl Acad Sci U S A 105:7803-8. 2008..Thus, NOD2 plays a key role in the B. anthracis-induced inflammatory response by being a critical mediator of IL-1beta secretion... - Allergen-induced peribronchial fibrosis and mucus production mediated by IkappaB kinase beta-dependent genes in airway epitheliumDavid H Broide
Department of Medicine, Laboratory of Gene Regulation and Signal Transduction, University of California at San Diego, La Jolla, CA 92093, USA
Proc Natl Acad Sci U S A 102:17723-8. 2005..Overall, these studies show an important role for NF-kappaB regulated genes in airway epithelium in allergen-induced airway remodeling, including peribronchial fibrosis and mucus production... - Genetic and pharmacological inhibition of JNK ameliorates hypoxia-induced retinopathy through interference with VEGF expressionMonica Guma
Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, School of Medicine, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093 0723, USA
Proc Natl Acad Sci U S A 106:8760-5. 2009..These results strongly suggest that JNK1 plays a key role in retinal neoangiogenesis and that it represents a new pharmacological target for treatment of diseases where excessive neoangiogenesis is the underlying pathology... - Epithelial cell I kappa B-kinase beta has an important protective role in Clostridium difficile toxin A-induced mucosal injurySungwon Chae
Department of Medicine, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA
J Immunol 177:1214-20. 2006..difficile toxin A exposure that is mediated, at least in part, through promoting epithelial cell survival by abrogating epithelial cell apoptosis... - Anthrax toxin induces macrophage death by p38 MAPK inhibition but leads to inflammasome activation via ATP leakageSyed Raza Ali
Laboratory of Signal Transduction, Department of Pharmacology, University of California, San Diego, La Jolla, California, USA
Immunity 35:34-44. 2011..Prevention of cell death or ATP release through constitutive p38 or AKT activation interfered with inflammasome activation and IL-1β production, thereby compromising antimicrobial immunity... - Opposing functions of IKKbeta during acute and chronic intestinal inflammationLars Eckmann
Department of Medicine, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA
Proc Natl Acad Sci U S A 105:15058-63. 2008..Our findings caution against the therapeutic use of IKKbeta/NF-kappaB inhibitors in acute inflammatory settings dominated by cell loss and ulceration... - Activation of the E3 ubiquitin ligase Itch through a phosphorylation-induced conformational changeEwen Gallagher
Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, School of Medicine, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093 0723, USA
Proc Natl Acad Sci U S A 103:1717-22. 2006.... - Fibroblast-specific protein 1 identifies an inflammatory subpopulation of macrophages in the liverChristoph H Osterreicher
Department of Medicine, University of California at San Diego, La Jolla, CA 92093, USA
Proc Natl Acad Sci U S A 108:308-13. 2011..These findings suggest that FSP1 is a marker of a specific subset of inflammatory macrophages in liver injury, fibrosis, and cancer... - Reactive oxygen species promote TNFalpha-induced death and sustained JNK activation by inhibiting MAP kinase phosphatasesHideaki Kamata
Laboratory of Gene Regulation and Signal Transduction, School of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA
Cell 120:649-61. 2005..Antioxidant treatment also prevents TNFalpha-mediated fulminant liver failure without affecting liver regeneration... - IkappaB kinase alpha kinase activity is required for self-renewal of ErbB2/Her2-transformed mammary tumor-initiating cellsYixue Cao
Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, School of Medicine, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093 0723, USA
Proc Natl Acad Sci U S A 104:15852-7. 2007..IKKalpha may represent a novel and specific target for treatment of ErbB2-positive breast cancer... - NF-kappaB as a critical link between inflammation and cancerMichael Karin
Department of Pharmacology and Pathology, Moores Cancer Canter, UCSD School of Medicine, La Jolla, California 92093 0723, USA
Cold Spring Harb Perspect Biol 1:a000141. 2009..Most importantly, through its ability to up-regulate the expression of tumor promoting cytokines, such as IL-6 or TNF-alpha, and survival genes, such as Bcl-X(L), NF-kappaB provides a critical link between inflammation and cancer... - B-cell activating factor and v-Myc myelocytomatosis viral oncogene homolog (c-Myc) influence progression of chronic lymphocytic leukemiaWeizhou Zhang
Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, School of Medicine, Moores Cancer Center, University of California at San Diego, La Jolla, CA 92093, USA
Proc Natl Acad Sci U S A 107:18956-60. 2010.... - The two faces of IKK and NF-kappaB inhibition: prevention of systemic inflammation but increased local injury following intestinal ischemia-reperfusionLee Wei Chen
Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, University of California, San Diego, California, USA
Nat Med 9:575-81. 2003..These results show the dual function of the NF-kappaB system, which is responsible for both tissue protection and systemic inflammation, and underscore the caution that should be exerted in using NF-kappaB and IKK inhibitors... - Streptolysin O promotes group A Streptococcus immune evasion by accelerated macrophage apoptosisAnjuli M Timmer
Department of Pediatrics, Biomedical Sciences Graduate Program, Laboratory of Signal Transduction, University of California, San Diego, La Jolla, California 92093, USA
J Biol Chem 284:862-71. 2009..We conclude that accelerated, caspase-dependent macrophage apoptosis induced by the pore-forming cytolysin SLO contributes to GAS immune evasion and virulence... - Inflammation and colon cancerJanos Terzic
Laboratory of Gene Regulation and Signal Transduction, Departments of Pharmacology and Pathology, School of Medicine, University of California, San Diego, La Jolla, California, USA
Gastroenterology 138:2101-2114.e5. 2010..These mechanisms, as well as new approaches to prevention and therapy, are discussed in this review... - CK2 Is a C-Terminal IkappaB Kinase Responsible for NF-kappaB Activation during the UV ResponseTomohisa Kato
Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, School of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA
Mol Cell 12:829-39. 2003..Inhibition of this pathway prevents UV-induced IkappaBalpha degradation and increases UV-induced cell death. Thus, the p38-CK2-NF-kappaB axis is an important component of the mammalian UV response... - IKK beta is required for peripheral B cell survival and proliferationZhi Wei Li
Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, Cancer Center, University of California San Diego, La Jolla, CA 92093, USA
J Immunol 170:4630-7. 2003..Thus, IKKbeta provides a requisite role in B cell activation and maintenance and thus is a key determinant of humoral immunity... - Amino-terminal phosphorylation of c-Jun regulates apoptosis in the retinal ganglion cells by optic nerve transectionKazuhiko Yoshida
Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, University of California San Diego, La Jolla, CA, USA
Invest Ophthalmol Vis Sci 43:1631-5. 2002..To examine the involvement of c-Jun and c-Jun N-terminal phosphorylation (JNP) in apoptosis of retinal ganglion cells (RGCs) after the optic nerve (ON) transection... - Inflammatory cytokines in cancer: tumour necrosis factor and interleukin 6 take the stageSergei I Grivennikov
Laboratory of Gene Regulation and Signal Transduction, Departments of Pharmacology and Pathology, School of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA
Ann Rheum Dis 70:i104-8. 2011..The role of TNF and IL-6 as master regulators of tumour-associated inflammation and tumourigenesis makes them attractive targets for adjuvant treatment in cancer... - Nuclear cytokine-activated IKKalpha controls prostate cancer metastasis by repressing MaspinJun Li Luo
Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology and Cancer Center, School of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, California 92093 0723, USA
Nature 446:690-4. 2007..We propose that tumour-infiltrating RANKL-expressing cells lead to nuclear IKKalpha activation and inhibition of Maspin transcription, thereby promoting the metastatic phenotype... - Activation by IKKalpha of a second, evolutionary conserved, NF-kappa B signaling pathwayU Senftleben
Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA
Science 293:1495-9. 2001..IKKalpha is therefore a pivotal component of a second NF-kappaB activation pathway based on regulated NF-kappaB2 processing rather than IkappaB degradation... - c-Jun N-terminal kinase is required for metalloproteinase expression and joint destruction in inflammatory arthritisZ Han
Division of Rheumatology, Allergy and Immunology, University of California, San Diego, School of Medicine, La Jolla, California 92093, USA
J Clin Invest 108:73-81. 2001..Therefore, JNK is a critical MAPK pathway for IL-1--induced collagenase gene expression in synoviocytes and in joint arthritis, indicating that JNK is an important therapeutic target for RA... - IkappaB kinase-alpha acts in the epidermis to control skeletal and craniofacial morphogenesisAlok K Sil
Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, School of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, California 92093-0636, USA
Nature 428:660-4. 2004.... - NOD2 and Crohn's disease: loss or gain of function?Lars Eckmann
Department of Medicine, UCSD School of Medicine, La Jolla, California 92093, USA
Immunity 22:661-7. 2005..This review focuses on recent insights into the functions of normal and variant NOD2 proteins and the pathogenetic mechanisms underlying NOD2-associated inflammatory diseases... - NF-kappaB and cancer: mechanisms and targetsMichael Karin
Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, University of California San Diego, School of Medicine, La Jolla, California 92093, USA
Mol Carcinog 45:355-61. 2006..Importantly, NF-kappaB and the signaling pathways that mediate its activation have become attractive targets for development of new chemopreventive and chemotherapeutic approaches... - The carboxyl-terminal region of IkappaB kinase gamma (IKKgamma) is required for full IKK activationConstantin Makris
Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, University of California, San Diego, La Jolla 92093 0636, USA
Mol Cell Biol 22:6573-81. 2002..These results may explain why cells that express these or similar mutant alleles are sensitive to TNF-alpha-induced apoptosis despite being able to activate NF-kappaB in response to other stimuli... - Targeting of TAK1 by the NF-kappa B protein Relish regulates the JNK-mediated immune response in DrosophilaJin Mo Park
Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, School of Medicine, University of California, San Diego, La Jolla, 92093-0636, USA
Genes Dev 18:584-94. 2004..Because the IKK-NF-kappa B module also negatively regulates JNK activation in mammals, thereby controlling inflammation-induced apoptosis, the regulatory cross-talk between the JNK and NF-kappa B pathways appears to be broadly conserved... - JNK1 is required for maintenance of neuronal microtubules and controls phosphorylation of microtubule-associated proteinsLufen Chang
Laboratory of Gene Regulation and Signal Transduction, University of California, San Diego, School of Medicine, La Jolla, CA 92037, USA
Dev Cell 4:521-33. 2003..These results suggest that JNK1 is required for maintaining the cytoskeletal integrity of neuronal cells and is a critical regulator of MAP activity and MT assembly... - DNA-PKcs is required for activation of innate immunity by immunostimulatory DNAW Chu
The Sam and Rose Stein Institute for Research on Aging, University of California, San Diego 9500 Gilman Drive 92093, La Jolla, CA, USA
Cell 103:909-18. 2000..ISS-ODN and bacterial DNA activate DNA-PK, which in turn contributes to activation of IKK and NF-kappaB. These results reveal a novel role of DNA-PKcs in innate immune responses and a link between DNA repair and innate immunity... - p38 and extracellular signal-regulated kinases regulate the myogenic program at multiple stepsZ Wu
Laboratory of Gene Regulation and Signal Transduction, University of California, San Diego, La Jolla, California 92093 0322, USA
Mol Cell Biol 20:3951-64. 2000..Importantly, activation of ERK is inhibitory toward myogenic transcription in myoblasts but contributes to the activation of myogenic transcription and regulates postmitotic responses (i.e., hypertrophic growth) in myotubes... - Mapping of the inducible IkappaB phosphorylation sites that signal its ubiquitination and degradationJ Didonato
Department of Pharmacology, Program in Biomedical Science, University of California, San Diego School of Medicine, La Jolla, USA
Mol Cell Biol 16:1295-304. 1996..As substitution of a conserved lysine residue slows down the ubiquitination and degradation of IkappaBalpha without affecting its phosphorylation, polyubiquitination is required for inducible IkappaB degradation... - AP-1 function and regulationM Karin
Department of Pharmacology, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093 0636, USA
Curr Opin Cell Biol 9:240-6. 1997..In addition to regulation by heterodimerization between Jun, Fos and ATF proteins, AP-1 activity is regulated through interactions with specific protein kinases and a variety of transcriptional coactivators... - The NF-kappa B activation pathway: a paradigm in information transfer from membrane to nucleusD M Rothwarf
Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, University of California, San Diego, CA 92093 0636, USA
Sci STKE 1999:RE1. 1999.... - The IKK/NF-kappa B pathwayUwe Senftleben
Laboratory of Gene Regulation and Signal Transduction, The Department of Pharmacology, University of California, San Diego, La Jolla, CA 92093-0636, USA
Crit Care Med 30:S18-26. 2002 - Joint damage and inflammation in c-Jun N-terminal kinase 2 knockout mice with passive murine collagen-induced arthritisZuoning Han
University of California San Diego School of Medicine, La Jolla 92093, USA
Arthritis Rheum 46:818-23. 2002..The present study was undertaken to investigate whether selective loss of JNK-2 function decreases joint destruction in JNK-2 knockout mice, in order to determine the role of this isoform in inflammatory arthritis... - Nuclear export of NF90 is required for interleukin-2 mRNA stabilizationJaekyung Shim
Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, University of California, San Diego, La Jolla, CA 92093, USA
Mol Cell 10:1331-44. 2002..In nonstimulated cells, NF90 is mostly nuclear, but T cell activation results in its accumulation in the cytoplasm. The nuclear export of NF90 is required for IL-2 mRNA stabilization... - From death receptor to reactive oxygen species and c-Jun N-terminal protein kinase: the receptor-interacting protein 1 odysseyVladislav Temkin
Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, School of Medicine, University of California San Diego, La Jolla, CA, USA
Immunol Rev 220:8-21. 2007..These molecular mechanisms may be involved in neoplastic, autoimmune, neurodegenerative, inflammatory, and metabolic diseases... - Inflammation and oncogenesis: a vicious connectionSergei I Grivennikov
Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, School of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA
Curr Opin Genet Dev 20:65-71. 2010..Molecular and cellular pathways, which connect inflammation and cancer, have emerged as attractive targets for prevention and therapy. In this review we discuss general mechanisms and concepts of cancer promoting inflammation... - The two NF-kappaB activation pathways and their role in innate and adaptive immunityGiuseppina Bonizzi
Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, School of Medicine, University of California-San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0636, USA
Trends Immunol 25:280-8. 2004 - Inhibition of IkappaB kinase by a new class of retinoid-related anticancer agents that induce apoptosisYolanda Bayon
Sidney Kimmel Cancer Center, Department of Pharmacology, University of California-San Diego School of Medicine, San Diego, California, USA
Mol Cell Biol 23:1061-74. 2003..Thus, the presence of an excess of retinoic acid or a retinoid antagonist did not prevent the inhibition of IKK activation by MX781 and CD2325, indicating a retinoid receptor-independent mechanism of action... - IKKalpha, a critical regulator of epidermal differentiation and a suppressor of skin cancerPascal Descargues
Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, Cancer Center, School of Medicine, University of California, San Diego, La Jolla, CA 92093 0723, USA
EMBO J 27:2639-47. 2008..Although these are not the only functions of nuclear IKKalpha, this multifunctional protein is a key regulator of keratinocyte and epidermal differentiation and a critical suppressor of skin cancer... - The IkappaB kinase complex (IKK) contains two kinase subunits, IKKalpha and IKKbeta, necessary for IkappaB phosphorylation and NF-kappaB activationE Zandi
Department of Pharmacology, University of California at San Diego, La Jolla 92093 0636, USA
Cell 91:243-52. 1997..While the interactions between IKKalpha and IKKbeta may be mediated through their leucine zipper motifs, their helix-loop-helix motifs may be involved in interactions with essential regulatory subunits... - c-Fos transcriptional activity stimulated by H-Ras-activated protein kinase distinct from JNK and ERKT Deng
Department of Pharmacology, University of California at San Diego School of Medicine, La Jolla 92093 0636
Nature 371:171-5. 1994..Therefore, at least three types of proline-directed kinases transmit Ras- and mitogen-generated signals to the transcriptional machinery... - Abnormal morphogenesis but intact IKK activation in mice lacking the IKKalpha subunit of IkappaB kinaseY Hu
Department of Pharmacology, Cancer Center, University of California San Diego, La Jolla, CA 92093 0636, USA
Science 284:316-20. 1999..Instead, loss of IKKalpha interfered with multiple morphogenetic events, including limb and skeletal patterning and proliferation and differentiation of epidermal keratinocytes... - ATM is required for IkappaB kinase (IKKk) activation in response to DNA double strand breaksN Li
Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, University of California at San Diego, La Jolla, California 92093-0636, USA
J Biol Chem 276:8898-903. 2001..DNA-dependent protein kinase, another member of the PI3K-like family, PI3K itself, and c-Abl, a nuclear tyrosine kinase, are not required for this response... - Transactivation by NF-IL6/LAP is enhanced by phosphorylation of its activation domainC Trautwein
Department of Medicine, University of California, San Diego
Nature 364:544-7. 1993..We now show that stimulation of the protein kinase C pathway increases the phosphorylation of Ser 105 within the activation domain of NF-IL6/LAP, and enhances its transcriptional efficacy...
Research Grants
- Regulation of NF-kapaB and IKK by proinflammatory stimuliMichael Karin; Fiscal Year: 2010..As before these studies will advance both our basic understanding of IKK signaling as well as its varied and wide-reaching pathophysiological functions. ..
- Stress Signaling Pathways in Toxicity and DiseaseMichael Karin; Fiscal Year: 2010..To accomplish these aims we will use a combination of cellular biochemistry, molecular genetics and experimental pathology, an approach that has been proven effective during the previous project period. ..
- How Anthrax lethal factor kills macrophagesMichael Karin; Fiscal Year: 2007..Interference with this activation process may be used to increase host resistance to bacterial infections, both with agents of bioterrorism and more common pathogens. ..
- INTERACTIONS OF HEAVY METAL IONS WITH THE HUMAN GENOMEMichael Karin; Fiscal Year: 2007..As NF-KB plays a key role in inflammation, understanding the regulation of IKK activity by oxidants, such as ozone, will provide a molecular basis for oxidant induced inflammatory disease. ..
- Regulation of NF-kB and IKK by proinflammatory stimuliMichael Karin; Fiscal Year: 2007..abstract_text> ..
- Functions and Mechanisms of Radiation Induced ResponsesMichael Karin; Fiscal Year: 2006..abstract_text> ..
- Stress Activated Protein Kinases as Mediators of DiseaseMichael Karin; Fiscal Year: 2006..Collectively, these studies will provide a molecular framework for understanding how environmental factors communicate with genetic determinants to elicit major degenerative, metabolic and chronic inflammatory diseases. ..
- Regulation of NF-kB and IKK by proinflammatory stimuliMichael Karin; Fiscal Year: 2006..abstract_text> ..
- Role of inflammation in tumor promotion and progressionMichael Karin; Fiscal Year: 2010..While providing new information on the role of inflammation in carcinogenesis and tumor progression, this work can lead to development of chemopreventive and therapeutic strategies based on inhibition of necrosis-induced inflammation. ..
- IKK<alpha> and the control of prostate cancer metastasisMichael Karin; Fiscal Year: 2009....
- Pulmonary inflammation and lung cancer development and progressionMichael Karin; Fiscal Year: 2010....
- IKK<alpha> and the control of prostate cancer metastasisMichael Karin; Fiscal Year: 2010....
- Role of inflammation in tumor promotion and progressionMichael Karin; Fiscal Year: 2010....
- Regulation of NF-kapaB and IKK by proinflammatory stimuliMichael Karin; Fiscal Year: 2010....
- Stress Signaling Pathways in Toxicity and DiseaseMichael Karin; Fiscal Year: 2009..To accomplish these aims we will use a combination of cellular biochemistry, molecular genetics and experimental pathology, an approach that has been proven effective during the previous project period. ..
- ROLE OF PROTEIN KINASES AND UV INDUCED STRESS RESPONSEMichael Karin; Fiscal Year: 2001..These studies should shed new light on the mechanisms underlying cellular responses to UV radiation. These studies will also contribute to understanding how cells respond to other forms of radiation. ..
- AP-1 AS A XENOBIOTIC RECEPTORMichael Karin; Fiscal Year: 1993..These studies should provide a detailed molecular understanding of the mechanisms by which redox active xenobiotics affect gene expression and act as tumor promoters...
- AP-1 AS A XENOBIOTIC RECEPTORMichael Karin; Fiscal Year: 2001....
- How Anthrax lethal factor kills activated macrophagesMichael Karin; Fiscal Year: 2003..anthracis and its host, this project should enable the design of new therapeutic strategies that will tilt the balance in favor of the host macrophage in the battle against B. anthracis and inhalation anthrax. ..
- REGULATION OF NFKB AND IKK BY PROINFLAMMATORY STIMULIMichael Karin; Fiscal Year: 2002..He will investigate the signaling pathways leading from the IL-1 and TNF receptors to IKK by focusing on events occurring downstream to the recruitment of TRAF signal transducers. ..
- Stress Signaling Pathways in Toxicity and DiseaseMichael Karin; Fiscal Year: 2007..To accomplish these aims we will use a combination of cellular biochemistry, molecular genetics and experimental pathology, an approach that has been proven effective during the previous project period. ..