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CEA expression heterogeneity and plasticity confer resistance to the CEA-targeting bispecific immunotherapy antibody cibisatamab (CEA-TCB) in patient-derived colorectal cancer organoids.
(BMJ PUBLISHING GROUP, 2019-03-21)
BACKGROUND: The T cell bispecific antibody cibisatamab (CEA-TCB) binds Carcino-Embryonic Antigen (CEA) on cancer cells and CD3 on T cells, which triggers T cell killing of cancer cell lines expressing moderate to high ...
Solution NMR assignment of the ARC4 domain of human tankyrase 2.
(SPRINGER, 2019-04-15)
Tankyrases are poly(ADP-ribose)polymerases (PARPs) which recognize their substrates via their ankyrin repeat cluster (ARC) domains. The human tankyrases (TNKS/TNKS2) contain five ARCs in their extensive N-terminal region; ...
Genomic and Transcriptomic Determinants of Therapy Resistance and Immune Landscape Evolution during Anti-EGFR Treatment in Colorectal Cancer.
(CELL PRESS, 2019-06-26)
Despite biomarker stratification, the anti-EGFR antibody cetuximab is only effective against a subgroup of colorectal cancers (CRCs). This genomic and transcriptomic analysis of the cetuximab resistance landscape in 35 RAS ...
ADP-ribosyltransferases, an update on function and nomenclature.
(WILEY, 2021-07-29)
ADP-ribosylation, a modification of proteins, nucleic acids, and metabolites, confers broad functions, including roles in stress responses elicited, for example, by DNA damage and viral infection and is involved in intra- ...
Reconstitution of the destruction complex defines roles of AXIN polymers and APC in β-catenin capture, phosphorylation, and ubiquitylation.
(CELL PRESS, 2021-08-19)
The Wnt/β-catenin pathway is a highly conserved, frequently mutated developmental and cancer pathway. Its output is defined mainly by β-catenin's phosphorylation- and ubiquitylation-dependent proteasomal degradation, ...
Structural basis of tankyrase activation by polymerization.
(NATURE PORTFOLIO, 2022-12-01)
The poly-ADP-ribosyltransferase tankyrase (TNKS, TNKS2) controls a wide range of disease-relevant cellular processes, including WNT-β-catenin signalling, telomere length maintenance, Hippo signalling, DNA damage repair and ...
AXIN Shapes Tankyrase ARChitecture.
(CELL PRESS, 2016-10-04)
The poly(ADP-ribose)polymerase (PARP) Tankyrase uses ankyrin repeat modules to capture substrates via Tankyrase-binding peptide motifs. In this issue of Structure, Eisemann et al. (2016) describe how the signaling protein ...
Genome-wide and high-density CRISPR-Cas9 screens identify point mutations in PARP1 causing PARP inhibitor resistance.
(NATURE PUBLISHING GROUP, 2018-05-01)
Although PARP inhibitors (PARPi) target homologous recombination defective tumours, drug resistance frequently emerges, often via poorly understood mechanisms. Here, using genome-wide and high-density CRISPR-Cas9 ...
Structural Basis for Auto-Inhibition of the NDR1 Kinase Domain by an Atypically Long Activation Segment.
(CELL PRESS, 2018-08-07)
The human NDR family kinases control diverse aspects of cell growth, and are regulated through phosphorylation and association with scaffolds such as MOB1. Here, we report the crystal structure of the human NDR1 kinase ...
Regulation of Protein Interactions by Mps One Binder (MOB1) Phosphorylation.
(AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC, 2017-06-01)
MOB1 is a multifunctional protein best characterized for its integrative role in regulating Hippo and NDR pathway signaling in metazoans and the Mitotic Exit Network in yeast. Human MOB1 binds both the upstream kinases ...