Gain of function in linc-133 compensates for daf-18/PTEN loss and rescues survival

DAF-18, homology of PTEN, possess tumor suppressor activity. Loss of daf-18 causes cell growth in L1 diapause C. elegans is well studied; however, the reason why survival is dramatically shortened is not well elaborated. We found that linc-133 gain of function can fully restore the shortened survival caused by daf-18 loss. When lipid phosphatase activity of DAF-18 is defective, the linc-133 gain of function interacts with 14-3-3 proteins to obstruct DAF-16 translocation from the nucleus to the cytoplasm. However, the dysfunction of protein phosphatase activity of DAF-18 caused high levels of aggregated proteins. The linc-133 gain of function can induce HSP chaperones to select and process the aggregated proteins for degradation through ubiquitination. Our work demonstrates that protein homeostasis controlled by the protein phosphatase activity of DAF-18 is the main factor affecting survival and identifies a new function of the linc-133 gene, which can compensate for the loss of daf-18.