Cancer‐Associated BCL‐2 Mutants Reveal Mechanisms Towards Venetoclax Resistance
Venetoclax (VEN) resistance in chronic lymphocytic leukemia arises from diverse BCL2 mutations. We map mechanisms contributing to VEN resistance across common BCL‐2 variants. G101V and D103Y reduce drug binding and increase sequestration of pro‐apoptotic proteins. V156D blocks VEN allosterically.
Jonas Aufdermauer +9 more
wiley +1 more source
Site-directed mutagenesis reveals the interplay between stability, structure, and enzymatic activity in RidA from Capra hircus. [PDF]
Rizzi G +8 more
europepmc +1 more source
ADORA2A activation suppresses NFκB‐dependent CCL5 production in cNK cells during chronic HBV infection, disrupting intrahepatic DC recruitment and HBV‐specific CD8+ T‐cell differentiation and function. Targeting the ADORA2A/NFκB/CCL5 axis restores antiviral immunity and facilitates HBV clearance.
Ailu Yang +9 more
wiley +1 more source
Characterization of Three Types of Elongases from Different Fungi and Site-Directed Mutagenesis. [PDF]
Wang Y +5 more
europepmc +1 more source
In PWS‐ASPCs, FOSL1 drives the expression of SPSB1. SPSB1, as part of the ESC complex, further binds to HDAC1 and promotes K29‐linked and K48‐linked polyubiquitination of HDAC1. These modifications facilitate the degradation of HDAC1 through the ALP and UPS pathways, respectively.
Hongrui Chen +5 more
wiley +1 more source
Addressing the Evolution of Cardenolide Formation in Iridoid-Synthesizing Plants: Site-Directed Mutagenesis of PRISEs (Progesterone-5β-Reductase/Iridoid Synthase-like Enzymes) of Plantago Species. [PDF]
Dorfner M +5 more
europepmc +1 more source
Model illustrating the proposed mechanism by which chemotherapy‐induced downregulation of OGT disrupts SNAP29 O‐GlcNAcylation, promoting STX17‐SNAP29‐VAMP8 SNARE complex assembly and protective autophagy, leading to chemoresistance, which in turn establishes a feedforward loop to perpetuate drug tolerance.
Liang Tang +9 more
wiley +1 more source
Codeine 3-O-demethylase catalyzed biotransformation of morphinan alkaloids in Escherichia coli: site directed mutagenesis of terminal residues improves enzyme expression, stability and biotransformation yield. [PDF]
Spencer GWK +5 more
europepmc +1 more source
This study identifies that the PD‐associated TMEM175‐L156P variant disrupts lysosomal ion channel trafficking by causing aberrant endoplasmic reticulum retention. A “chaperone–agonist” bifunctional small molecule restores TMEM175‐L156P lysosomal localization and channel function, thereby alleviating PD‐relevant cellular phenotypes and highlighting a ...
Ting Luo +17 more
wiley +1 more source
Controlling DNA Fragments Translocation across Nanopores with the Synergic Use of Site-Directed Mutagenesis, pH-Dependent Charge Tuning, and Electroosmotic Flow. [PDF]
Mereuta L +6 more
europepmc +1 more source

