Abstract
AbstractDAF-18, homology of PTEN, possess tumor suppressor activity. Loss ofdaf-18causes cell growth in L1 diapauseC. elegansis well studied; however, the reason why survival is dramatically shortened is not well elaborated. We found thatlinc-133gain of function can fully restore the shortened survival caused bydaf-18loss. When lipid phosphatase activity of DAF-18 is defective, thelinc-133gain 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. Thelinc-133gain 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 thelinc-133gene, which can compensate for the loss ofdaf-18.
Publisher
Cold Spring Harbor Laboratory