A novel gain-of-function mutation in partially suppresses mTORC2 defects.

The serine/threonine protein kinase SGK-1 is a downstream target of mTOR complex 2 (mTORC2) and is a conserved regulator of growth and metabolism. In , mutations in , which encodes an essential component of mTORC2, impairs lipid homeostasis and growth; however, these defects are partially suppressed by an activating mutation in SGK-1 , E116K. Here, we describe a stronger gain-of-function mutation in , L112F, that was identified in a forward genetic screen for suppressor mutations This allele will be useful in further dissecting the mTORC2 pathway and provides new insight into the role of this conserved residue in regulating SGK-1 kinase activity.

Mutations in nucleotide metabolism genes bypass proteasome defects in png-1/NGLY1-deficient Caenorhabditis elegans.

The conserved SKN-1A/Nrf1 transcription factor regulates the expression of proteasome subunit genes and is essential for maintenance of adequate proteasome function in animal development, aging, and stress responses. Unusual among transcription factors, SKN-1A/Nrf1 is a glycoprotein synthesized in the endoplasmic reticulum (ER). N-glycosylated SKN-1A/Nrf1 exits the ER and is deglycosylated in the cytosol by the PNG-1/NGLY1 peptide:N-glycanase.

The F-box protein FBXL-5 governs vitellogenesis and lipid homeostasis in .

The molecular mechanisms that govern the metabolic commitment to reproduction, which often occurs at the expense of somatic reserves, remain poorly understood. We identified the F-box protein FBXL-5 as a negative regulator of maternal provisioning of vitellogenin lipoproteins, which mediate the transfer of intestinal lipids to the germline. Mutations in partially suppress the vitellogenesis defects observed in the heterochronic mutants and both of which ectopically express at the adult developmental stage.