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MICHAEL KARIN 858-534-0872
FAX: 858-534-8158
email: mailto:karinoffice@ucsd.edu
Ph.D., University of California, Los Angeles,
Los Angeles, Professor of Pharmacology
Key Words: Gene Expression, Signal
Transduction, Transcription Factors,
Oncogenes, Protein Kinases
1) Regulation of transcription in mammalian cells by steroid hormones, growth factors, adverse environmental conditions and during cellular differentiation. Biochemical and genetic approaches are utilized to isolate transacting regulatory proteins which mediate the responses to developmental, hormonal and environmental signals by binding to specific DNA sequences. Our major efforts are to understand the regulation of transcription by growth factors and polypeptide hormones and cell type specific gene expression. Thus we are looking at the regulation of transcription factor activity by signal transduction pathways. 2) Response of the human genome to stress. The molecular basis for the UV response, the mammalian counterpart of the bacterial SOS response, is being studied by various molecular genetics techniques. 3) Cell type specific gene expression and molecular basis for differentiation. We study the molecular and genetic control of anterior pituitary development with special emphasis on the hierarchy of transcription factors involved in formation of growth hormone and prolactin-expressing cells. 4) Protein kinase cascades and their role in growth control, cell differentiation and programmed cell death.
Selected Publications:
Liu, Z-G, Hu H, Goeddel DV, Karin M. 1996. Section of TNF receptor 1 effector functions: JNK activation is not linked to apoptosis, while NF-k B activation prevents cell death. Cell 87:565-76.
DiDonato JA, Hayakawa M, Rothwarf DM, Zandi E, Karin M. 1997. A cytokine-responsive Ik B kinase that activates the transcription factor NF-k B. Nature 388:548-54.
Zandi E. Rothwarf DM, Delhase M, Hayakawa M, Karin M. 1997. The Ik B kinase complex (IKK) contains two kinase subunits, IKKa and IKKb , necessary for Ik B phosphorylation and NF-k B activation. Cell 91:243-52.
Chen C-Y, Del Gatto-Konczak F, Wu Z, Karin M. 1998. Stabilization of interleukin-2 mRNA by the c-Jun NH2-terminal kinase pathway. Science 280:1945-9.
Rothwarf DM, Zandi E, Natoli G, Karin M. 1998. IKKg is an essential regulatory subunit of the Ik B kinase complex. Nature 395:297-300.
Hu Y, Baud V, Delhase M, Zhang P, Deerinck T, Ellisman M, Johnson R, Karin M. 1999. Abnormal morphogenesis but intact IKK activation in mice lacking the IKKa subunit of the Ik B kinase. Science 284:316-20.
Baud V, Liu Z-G, Bennett B, Suzuki N, Xia Y, Karin M. 1999. Signaling by proinflammatory cytokines: oligomerization of TRAF2 and TRAF6 is sufficient for JNK and IKK activation and target gene induction via an N-terminal effector domain. Genes Dev 13:1297-1308.
Shaulian, E., Schreiber, M., Piu, F., Beeche, M., Wagner, E.F. and Karin, M. 2000. The mammalian UV response: c-Jun induction is required for exit from p53-imposed growth arrest. Cell. 103:897-907.
Hu, Y., Baud, V., Oga, T. Kim, K., Kazuhiko, Y. and Karin, M. 2001. IKKa controls formation of the epidermis independently of NF-k B via a differentiation inducing factor. Nature 410:710-714.
Senftleben, U., Cao, Y., Xiao, G., Greten, F., Krahn, G., Bonizzi, G., Chen, Y., Hu, Y., Fong, A., Sun, S., Karin, M. 2001. Activation by IKKa of a Second, Evolutionary Conserved, NF-k B Signaling Pathway. Science. In Press.
SCIENCE Manuscript Title:"Macrophage Apoptosis by Anthrax Lethal Factor Through Inhibition of p38 MAP Kinase"
Manuscript Number: 1073163 URL: http://www.sciencemag.org/cgi/content/abstract/1073163
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rof. Michael Karin, Ph.D.美国加州大学洛杉矶分校药理系University of California, Los Angeles, Professor of Pharmacology
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