Von dieser Seite existiert nur eine englische Version!

The main interest in my laboratory is directed towards understanding basic molecular mechanisms that control cell proliferation and malignant transformation. In particular we are interested to determine the regulation and function of proteins of the MYC/MAX/MAD network of transcriptional regulators. We are focusing on the mechanisms that are used by these proteins to control gene expression. Furthermore we are studying cofactors that are recruited by components of the network to mediate their activities, in particular in relation to chromatin structure, histone modification and polymerase activity. An additional focus is the analysis of downstream effectors, including different signal transduction pathways that are controlled by MYC and MAD proteins.

Ongoing projects include:

• We have identified PARP10, a novel member of the poly-ADP-ribose polymerase familie, as an interaction partner of MYC. We are now interested to understand the functional relevance of PARP10 for MYC-driven gene transcription.

• Cyclin E/CDK2 is a downstream effector of MYC. We have identified novel substrates of this kinase and are studying the function of these substrates and the consequences of their phosphorylation by Cyclin E/CDK2.

• We have cloned the promoter of the gene encoding the MYC antagonist MAD1. We are now addressing how cytokine signaling controls promoter activity.

• MAD1 interferes with different apoptotic signals. We are focusing on how MAD1 controls relevant target genes, including the PTEN gene, to inhibit apoptosis.

• We have described ASH2 as a protein with tumorigenic activity. Our present studies are designed to understand in more detail how this protein transforms cells.

 

Selected recent publications:

• Kleine, H., Poreba, E., Lesniewicz, K., Hassa, P. O., Hottiger, M. O., Litchfield, D. W., Shilton, B. H., and Lüscher, B. 2008. Substrate-assisted catalysis by PARP10 limits its activity to mono-ADP-ribosylation. Mol. Cell 32, 57-69.

• Pandithage*, R., Lilischkis*, R., Harting, K., Wolf, A., Jedamzik, B., Lüscher-Firzlaff, J., Vervoorts, J., Lasonder, E., Kremmer, E., Knöll*, B., and Lüscher*, B. 2008. The regulation of SIRT2 function by Cyclin-dependent kinases affects cell motility. J. Cell Biol. 180, 915-929. *equal contribution

•  Jiang, K., Hein*, N., Eckert*, K., Lüscher-Firzlaff, J, and Lüscher, B. 2008. Regulation of the MAD1 promoter by G-CSF. Nucl. Acids Res. 36. 1517-1531. *equal contribution 

• Lüscher-Firzlaff*, J., Gawlista*, I., Vervoorts, J., Kapelle, K., Braunschweig, T., Walsemann, G., Rodgarkia-Schamberger, C., Schuchlautz, H., Dreschers, S., Kremmer, E., Lilischkis, R., Cerni, C., Wellmann, A., Lüscher, B. 2008. The human trithorax protein hASH2 functions as an oncoprotein. Cancer Res. 68, 749-758. *equal contribution 

• Rottmann*, S. Speckgens*, S., Lüscher-Firzlaff, J. M., and Lüscher, B. 2008. Inhibition of apoptosis by MAD1 is mediated by repression of the PTEN tumor suppressor gene. FASEB Journal, 22, 1124-1134. *equal contribution 

• French, A.C., Lüscher, B., and Litchfield, D.W. 2007. Development of a stabilized form of the regulatory CK2 subunit that inhibits cell proliferation. J. Biol. Chem. 282, 29667-29677. 

• Guccione, E., Bassi, C., Casadio, F., Martinato, F., Cesaroni, M., Schuchlautz, H., Lüscher, B., and Amati, B. 2007. Methylation of histone H3R2 by PRMT6 and H3K4 by MLL complexes are mutually exclusive. Nature 449, 933-937. 

• Lue, H., Thiele, M., Franz, J., Dahl, E., Speckgens, S., Leng, L., Fingerle-Rowson, G., Bucala, R., Lüscher, B., and Bernhagen, J. 2007. Macrophage migration inhibitory factor (MIF) promotes cell survival by activation of the Akt pathway and role for CSN5/JAB1 in the control of autocrine MIF activity. Oncogene 26, 5046-5059. 

• Lüscher-Firzlaff, J. M., Lilischkis, R., and Lüscher, B. 2006. Regulation of the transcription factor FOXM1c by Cyclin E/CDK2. FEBS Lett. 580, 1716-1722. 

• Lesniewicz, K., Lüscher-Firzlaff, J., Poreba, E., Fuchs, P., Walsemann, G., Wiche, G., and Lüscher, B. 2005. Overlap of the gene encoding the novel poly(ADP-ribose) polymerase Parp10 with the plectin gene and common use of exon sequences. Genomics 86, 38-46. 

• Krippner-Heidenreich, A., Walsemann, G., Beyrouthy, M. J., Speckgens, S., Kraft, R., Thole, H., Talanian, R. V., Hurt, M. M., and Lüscher, B. 2005. Caspase-dependent regulation and subcellular redistribution of the transcriptional modulator YY1 during apoptosis. Mol. Cell. Biol. 25, 3704-3714. 

• Rottmann, S., Menkel, A. R., Bouchard, C., Mertsching, J., Loidl, P., Kremmer, E., Eilers, M., Lüscher-Firzlaff, J., Lilischkis, R., and Lüscher, B. 2005. Mad1 function in cell proliferation and transcriptional repression is antagonized by Cyclin E/CDK2. J. Biol. Chem. 280, 15489-15492 

• Yu, M., Schreek, S., Cerni, C., Schamberger, C., Lesniewicz, K., Poreba, E., Vervoorts, J., Walsemann, G., Grötzinger, J., Kremmer, E., Mehraein, Y., Mertsching, J., Kraft, R., Austen, M., Lüscher-Firzlaff, J., and Lüscher, B. 2005. PARP-10, a novel Myc-interacting protein with poly(ADP-ribose) polymerase activity, inhibits transformation. Oncogene 24, 1982-1993. 

• Vervoorts, J., Lüscher-Firzlaff, J. M., Rottmann, S., Lilischkis, R., Walsemann, G., Dohmann, K., Austen, M., and Lüscher, B. 2003. Stimulation of c-Myc transcriptional activity and acetylation by recruitment of the cofactor CBP. EMBO Reports, 4, 484-490. 

• Cerni, C., Srkzypek, B., Popov, N., Sasgary, S., Schmidt, G., Larsson, L.-G., Lüscher, B., and Henriksson, M. 2002. Mad1 inhibits in vivo growth of Myc/Ras transformed tumor cells. Oncogene 21, 447-459. 

• Hölzel, M., Kohlhuber, F., Schlosser, I., Hölzel, D., Lüscher, B., and Eick, D. 2001. Myc/Max/Mad regulate the frequency but not the duration of productive cell cycles. EMBO Reports 2, 1125-1132. 

• Bouchard, C., Dittrich, O., Kiermaier, A., Dohmann, K., Eilers, M., and Lüscher, B. 2001. Regulation of cyclin D2 gene expression by the Myc/Max/Mad network: Myc-dependent TRRAP recruitment and histone acetylation at the cyclin D2 promoter. Genes&Dev. 15, 2042-2047. 

• Krippner-Heidenreich, A., Talanian, R. V., Sekul, R., Kraft, R., Thole, H., Ottleben, H., and Lüscher, B. 2001. Targeting of the transcription factor Max during apoptosis: Phosphorylation-regulated cleavage by caspase-5 at an unusual glutamic acid in position P1. Biochem. J. 358, 705-715.

 

Recent reviews:

• Vervoorts, J. and Lüscher, B. 2008. Post-translational regulation of the tumor suppressor p27KIP1. Cell. Mol. Life Sci. 65, 3255-3264.

• Lüscher, B. and Larsson, L.-G. 2007. The world according to MYC. EMBO reports 8, 1110-1114. 

• Vervoorts, J., Lüscher-Firzlaff, J., and Lüscher, B. 2006. The Ins and Outs of MYC regulation by posttranslational mechanisms. J. Biol. Chem. 281, 34725-34729 

• Rottmann, S. and Lüscher, B. 2006. The Mad side of the Max network: antagonizing the function of Myc and more. Current Topics in Microbiology and Immunology 302, 63-122 

• Lüscher, B. 2001. Function and regulation of the transcription factors of the Myc/Max/Mad network. Gene 277, 1-14.