TY  - JOUR
AB  - MALT1 paracaspase is activated upon antigen receptor stimulation to promote lymphocyte activation. In addition, deregulated MALT1 protease activity drives survival of distinct lymphomas such as the activated B cell type of diffuse large B cell lymphoma (ABC-DLBCL). Here, we designed fluorophore or biotin-coupled activity based-probes (ABP) that covalently modify the active center of MALT1. MALT1-ABPs are exclusively labeling an active modified full length form of MALT1 upon T cell stimulation. Further, despite the CARMA1 requirement for initial MALT1 activation, the MALT1-ABPs show that protease activity is not confined to the high-molecular CARMA1-BCL10-MALT1 (CBM) complex. Using biotin-coupled ABPs, we developed a robust assay for sensitive and selective detection of active MALT1 in cell lines, primary lymphocytes, and DLBCL tumor biopsies. Taken together, MALT1-ABPs represent powerful chemical tools to measure cellular MALT1 activation, determine efficacy of small molecule inhibitors, and classify lymphomas based on MALT1 activity status.
AU  - Eitelhuber, A.C.
AU  - Vosyka, O.*
AU  - Nagel, D.
AU  - Bognar, M.
AU  - Lenze, D.*
AU  - Lammens, K.*
AU  - Schlauderer, F.*
AU  - Hlahla, D.
AU  - Hopfner, K.P.*
AU  - Lenz, G.*
AU  - Hummel, M.*
AU  - Verhelst, S.H.*
AU  - Krappmann, D.
C1  - 43055
C2  - 35999
CY  - Cambridge
SP  - 129-138
TI  - Activity-based probes for detection of active MALT1 paracaspase in immune cells and lymphomas.
JO  - Chem. Biol.
VL  - 22
IS  - 1
PB  - Cell Press
PY  - 2014
SN  - 1074-5521
ER  - 

TY  - JOUR
AB  - The ability to map patterns of gene expression noninvasively in living animals could have impact in many areas of biology. Reporter systems compatible with MRI could be particularly valuable, but existing strategies tend to lack sensitivity or specificity. Here we address the challenge of MRI-based gene mapping using the reporter enzyme secreted alkaline phosphatase (SEAP), in conjunction with a water-soluble metalloporphyrin contrast agent. SEAP cleaves the porphyrin into an insoluble product that accumulates at sites of enzyme expression and can be visualized by MRI and optical absorbance. The contrast mechanism functions in vitro, in brain slices, and in animals. The system also provides the possibility of readout both in the living animal and by postmortem histology, and it notably does not require intracellular delivery of the contrast agent. The solubility switch mechanism used to detect SEAP could be adapted for imaging of additional reporter enzymes or endogenous targets.
AU  - Westmeyer, G.G.
AU  - Emer, Y.*
AU  - Lintelmann, J.
AU  - Jasanoff, A.*
C1  - 30833
C2  - 33903
CY  - Cambridge
SP  - 422-429
TI  - MRI-based detection of alkaline phosphatase gene reporter activity using a porphyrin solubility switch.
JO  - Chem. Biol.
VL  - 21
IS  - 3
PB  - Cell Press
PY  - 2014
SN  - 1074-5521
ER  - 

TY  - JOUR
AB  - In this work, the biosynthesis and regulation of the polyketide synthase/nonribosomal peptide synthetase (PKS/NRPS)-derived mutagenic mycotoxin fusarin C was studied in the fungus Fusarium fujikuroi. The fusarin gene cluster consists of nine genes (fus1-fus9) that are coexpressed under high-nitrogen and acidic pH conditions. Chromatin immunoprecipitation revealed a correlation between high expression and enrichment of activating H3K9-acetylation marks under inducing conditions. We provide evidence that only four genes are sufficient for the biosynthesis. The combination of genetic engineering with nuclear magnetic resonance and mass-spectrometry-based structure elucidation allowed the discovery of the putative fusarin biosynthetic pathway. Surprisingly, we indicate that PKS/NRPS releases its product with an open ring structure, probably as an alcohol. Our data indicate that 2-pyrrolidone ring closure, oxidation at C-20, and, finally, methylation at C-20 are catalyzed by Fus2, Fus8, and Fus9, respectively.
AU  - Niehaus, E.-M.*
AU  - Kleigrewe, K.*
AU  - Wiemann, P.*
AU  - Studt, L.*
AU  - Sieber, C.M.K.
AU  - Connolly, L.R.*
AU  - Freitag, M.*
AU  - Güldener, U.
AU  - Tudzynski, B.*
AU  - Humpf, H.-U.*
C1  - 26599
C2  - 32295
SP  - 1055-1066
TI  - Genetic manipulation of the Fusarium fujikuroi fusarin gene cluster yields insight into the complex regulation and fusarin biosynthetic pathway.
JO  - Chem. Biol.
VL  - 20
IS  - 8
PB  - Cell Press
PY  - 2013
SN  - 1074-5521
ER  - 

TY  - JOUR
AU  - Kiessling, A.*
AU  - Sperl, B.*
AU  - Hollis, A.*
AU  - Eick, D.
AU  - Berg, T.*
C1  - 4982
C2  - 23760
SP  - 745-751
TI  - Selective inhibition of c-Myc/max dimerization and DNA binding by small molecules.
JO  - Chem. Biol.
VL  - 13
PY  - 2006
SN  - 1074-5521
ER  -