The N-degron pathway targets proteins that bear a destabilizing residue at the N terminus for proteasome-dependent degradation(1). In yeast, Ubr1-a single-subunit E3 ligase-is responsible for the Arg/N-degron pathway(2). How Ubr1 mediates the initiation of ubiquitination and the elongation of the ubiquitin chain in a linkage-specific manner through a single E2 ... More
FKBP10 promotes clear cell renal cell carcinoma progression and regulates sensitivity to the HIF2α blockade by facilitating LDHA phosphorylation.
Renal cell carcinoma (RCC) is one of the three major malignant tumors of the urinary system and originates from proximal tubular epithelial cells. Clear cell renal cell carcinoma (ccRCC) accounts for approximately 80% of RCC cases and is recognized as a metabolic disease driven by genetic mutations and epigenetic alterations. ... More
Increased levels of eIF2A inhibit translation by sequestering 40S ribosomal subunits.
AuthorsGrove DJ,Levine DJ,Kearse MG
JournalNucleic acids research
PubMed ID37602404
eIF2A was the first eukaryotic initiator tRNA carrier discovered but its exact function has remained enigmatic. Uncharacteristic of translation initiation factors, eIF2A is reported to be non-cytosolic in multiple human cancer cell lines. Attempts to study eIF2A mechanistically have been limited by the inability to achieve high yield of soluble ... More
Brain-enriched RagB isoforms regulate the dynamics of mTORC1 activity through GATOR1 inhibition.
Mechanistic target of rapamycin complex 1 (mTORC1) senses nutrient availability to appropriately regulate cellular anabolism and catabolism. During nutrient restriction, different organs in an animal do not respond equally, with vital organs being relatively spared. This raises the possibility that mTORC1 is differentially regulated in different cell types, yet little ... More