Chemical Biology
A new ferrocene derivative blocks K-Ras localization and function by oxidative modification at His95We report redox system regulates KRAS localization and activity via oxidation at His95 residue, and proposes a role of oncogenic K-Ras in the antioxidant-induced growth and metastasis of KRAS-driven cancers.
A novel antifolate suppresses growth of FPGS-deficient cells and overcomes methotrexate resistanceMechanistic characterization of a novel, lipophilic antifolate that suppresses growth of FPGS-deficient cells that are linked to methotrexate resistance and relapse in cancer patients.
FAT10 and NUB1L cooperate to activate the 26S proteasome26S proteasome activation is achieved by the collective binding of the ubiquitin-like modifier FAT10 and its interaction partner NUB1L, causing gate opening in a USP14-independent way.
Membrane cholesterol regulates inhibition and substrate transport by the glycine transporter, GlyT2Cholesterol binds to the GlyT2 SLC6 transporter, enhancing the effect of bioactive lipid analgesics, providing new therapeutic avenues to treat neuropathic pain and target SLC6 transporters.
An unconventional cancer-promoting function of methamphetamine in hepatocellular carcinomaMETH use is associated with a higher incidence of hepatocellular carcinoma (HCC) in METH abusers and rehabilitees. METH exposure promotes HCC progression by ROS-mediated activation of the Ras/MEK/ERK signaling pathway. Clearance of ROS by NAC abolishes METH-induced HCC progression.
The βI domain promotes active β1 integrin clustering into mature adhesion sitesMana et al show that the extracellular headpiece βI domain is involved in conformationally active β1 integrin clustering, fibrillar adhesion formation, incorporation of soluble fibronectin dimers into fibrillar polymers, and extracellular matrix–dependent endothelial cell migration.
SMA-linked SMN mutants prevent phase separation properties and SMN interactions with FMRP family membersThe survival motor neuron (SMN) protein associates with translation regulators and phase-separates into RNA-stabilized droplets that are likely candidates for the formation of nuclear and cytoplasmic membraneless organelles.
Tanshinone functions as a coenzyme that confers gain of function of NQO1 to suppress ferroptosisNQO1 catalyzes the reduction of tanshinones to detoxify lipid peroxyl radicals and inhibit ferroptosis both in vitro and in vivo, providing a molecular mechanism for the therapeutic effects of tanshinones, such as cardiac protection.
Non-canonical miRNA-RNA base-pairing impedes tumor suppressor activity of miR-16In uveal melanoma tumors, the RNA decay activity of the tumor suppressor miR-16 is impaired by sponge RNAs. These RNAs defined a powerful signature to predict overall survival.
Insight into the mechanism of DNA synthesis by human terminal deoxynucleotidyltransferaseThe role of metal ions and specific interactions of dNTP with active-site amino acid residues in the mechanisms underlying the recognition of nucleoside triphosphates by human terminal deoxynucleotidyltransferase were revealed by pre–steady-state kinetics and molecular dynamics approaches.