TY  - JOUR
A1  - Grimm, Clemens
A1  - Pelz, Jann-Patrick
A1  - Schneider, Cornelius
A1  - Schäffler, Katrin
A1  - Fischer, Utz
T1  - Crystal Structure of a Variant PAM2 Motif of LARP4B Bound to the MLLE Domain of PABPC1
JF  - Biomolecules
N2  - Eukaryotic cells determine the protein output of their genetic program by regulating mRNA transcription, localization, translation and turnover rates. This regulation is accomplished by an ensemble of RNA-binding proteins (RBPs) that bind to any given mRNA, thus forming mRNPs. Poly(A) binding proteins (PABPs) are prominent members of virtually all mRNPs that possess poly(A) tails. They serve as multifunctional scaffolds, allowing the recruitment of diverse factors containing a poly(A)-interacting motif (PAM) into mRNPs. We present the crystal structure of the variant PAM motif (termed PAM2w) in the N-terminal part of the positive translation factor LARP4B, which binds to the MLLE domain of the poly(A) binding protein C1 cytoplasmic 1 (PABPC1). The structural analysis, along with mutational studies in vitro and in vivo, uncovered a new mode of interaction between PAM2 motifs and MLLE domains.
KW  - PAM2w
KW  - PAM2
KW  - PABC1
KW  - MLLE domain
KW  - PABP
KW  - Poly(A) binding protein
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-207800
SN  - 2218-273X
VL  - 10
IS  - 6
ER  - 
TY  - JOUR
A1  - Weidner, Christopher
A1  - Rousseau, Morten
A1  - Plauth, Annabell
A1  - Wowro, Sylvia J.
A1  - Fischer, Cornelius
A1  - Abdel-Aziz, Heba
A1  - Sauer, Sascha
T1  - Iberis amara Extract Induces Intracellular Formation of Reactive Oxygen Species and Inhibits Colon Cancer
JF  - PLoS ONE
N2  - Massively increasing global incidences of colorectal cancer require efficient treatment and prevention strategies. Here, we report unexpected anticancerogenic effects of hydroethanolic Iberis amara extract (IAE), which is known as a widely used phytomedical product for treating gastrointestinal complaints. IAE significantly inhibited the proliferation of HT-29 and T84 colon carcinoma cells with an inhibitory concentration (IC\(_{50}\)) of 6 and 9 μg/ml, respectively, and further generated inhibitory effects in PC-3 prostate and MCF7 breast cancer cells. Inhibition of proliferation in HT-29 cells was associated with a G2/M phase cell cycle arrest including reduced expression of various regulatory marker proteins. Notably, in HT-29 cells IAE further induced apoptosis by intracellular formation of reactive oxygen species (ROS). Consistent with predictions derived from our in vitro experiments, bidaily oral gavage of 50 mg/kg of IAE over 4 weeks resulted in significant inhibition of tumor growth in a mouse HT-29 tumor xenograft model. Taken together, Iberis amara extracts could become useful alternatives for preventing and treating the progression of colon cancer.
KW  - iberis amara extract
KW  - colorectal cancer
KW  - treatment
KW  - prevention
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-167044
VL  - 11
IS  - 4
ER  - 
TY  - JOUR
A1  - Salehi, Saeede
A1  - Zare, Abdolhossein
A1  - Prezza, Gianluca
A1  - Bader, Jakob
A1  - Schneider, Cornelius
A1  - Fischer, Utz
A1  - Meissner, Felix
A1  - Mann, Matthias
A1  - Briese, Michael
A1  - Sendtner, Michael
T1  - Cytosolic Ptbp2 modulates axon growth in motoneurons through axonal localization and translation of Hnrnpr
JF  - Nature Communications
N2  - The neuronal RNA-binding protein Ptbp2 regulates neuronal differentiation by modulating alternative splicing programs in the nucleus. Such programs contribute to axonogenesis by adjusting the levels of protein isoforms involved in axon growth and branching. While its functions in alternative splicing have been described in detail, cytosolic roles of Ptbp2 for axon growth have remained elusive. Here, we show that Ptbp2 is located in the cytosol including axons and growth cones of motoneurons, and that depletion of cytosolic Ptbp2 affects axon growth. We identify Ptbp2 as a major interactor of the 3’ UTR of Hnrnpr mRNA encoding the RNA-binding protein hnRNP R. Axonal localization of Hnrnpr mRNA and local synthesis of hnRNP R protein are strongly reduced when Ptbp2 is depleted, leading to defective axon growth. Ptbp2 regulates hnRNP R translation by mediating the association of Hnrnpr with ribosomes in a manner dependent on the translation factor eIF5A2. Our data thus suggest a mechanism whereby cytosolic Ptbp2 modulates axon growth by fine-tuning the mRNA transport and local synthesis of an RNA-binding protein.
KW  - molecular neuroscience
KW  - RNA-binding proteins
KW  - RNA transport
Y1  - 2023
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-357639
VL  - 14
ER  -