Cell Biology
Defective nucleotide-dependent assembly and membrane fusion in Mfn2 CMT2A variants improved by BaxMfn2 CMT2A–associated variants located proximal to the hinge connecting its two extended helical bundles have impaired GTP-dependent assembly and mitochondrial fusion activity, which are both improved by cytosolic Bax.
CDKL3 promotes osteosarcoma progression by activating Akt/PKBThis study demonstrates that CDKL3 regulates Akt activation and its downstream targets to promote OS progression, creating a therapeutically targetable vulnerability in treatment of OS.
SLX4IP and telomere dynamics dictate breast cancer metastasis and therapeutic responsivenessAn unbiased genetic screen established SLX4IP as an essential driver of telomere maintenance mechanism identity, metastatic progression, and therapeutic response of breast cancers.
The iron–sulfur helicase DDX11 promotes the generation of single-stranded DNA for CHK1 activationThe iron–sulfur cluster helicase DDX11 promotes the generation of ssDNA and the phosphorylation of CHK1 at serine-345, possibly by unwinding replication-dependent DNA secondary structures.
Meiotic sex chromosome cohesion and autosomal synapsis are supported by Esco2This study reveals a role for the cohesin modifier ESCO2 for maintenance of sister chromatid cohesion in mammalian meiosis and a specific weakness of cohesion within male sex chromosome chromatin
Caspase-1 interdomain linker cleavage is required for pyroptosisThe related human NLRP1 and CARD8 form ASC-dependent and ASC-independent inflammasomes, respectively, both of which require pro-caspase-1 interdomain linker processing for the induction of pyroptosis.
The stress polarity signaling (SPS) pathway serves as a marker and a target in the leaky gut barrier: implications in aging and cancerUsing patient-derived organoids the authors show how a specialized polarity pathway protects our gut barrier from stress-induced collapse. Findings highlight both diagnostic and therapeutic potential of the pathway for treating gut barrier dysfunction in aging, cancer, and dysbiosis.
Essential role of the Crk family-dosage in DiGeorge-like anomaly and metabolic homeostasisThis study presents evidence that CRK/CRKL and TBX1 may share pathways that participate in organogenesis affected in DiGeorge syndrome (22q11.2DS) via global control of gene expression and metabolism
ER-resident sensor PERK is essential for mitochondrial thermogenesis in brown adipose tissueThe endoplasmic reticulum-resident sensor PERK is phosphorylated during brown adipocyte differentiation and is required for mitochondrial inner membrane protein biogenesis and thermogenic function.
Site-specific phosphorylation regulates the functions of kindlin-3 in a variety of cellsA new monoclonal antibody in combination with mutational analyses shows that a single serine phosphorylation in kindlin-3 is functionally important in both hematopoietic and non-hematopoietic cells.