Nahum Sonenberg - Translational control of Autism Spectrum Disorder and Fragile-X syndrome
Channel: Institut des Hautes Études Scientifiques (IHÉS)
Date: 2018-03-27

Translational  control  plays  a critical  role  in  essential  cellular  processes  including  cell  growth, proliferation,  development,  and  learning  and  memory.  Under  most  circumstances,  translational 
control is exerted at the initiation step in which the eukaryotic translation initiation factor 4E (eIF4E) interacts with the mRNA 5’cap structure to facilitate the recruitment of ribosomes and promote translation. Importantly, eIF4E preferentially stimulates the translation of a subset of mRNAs. The activity  of  eIF4E  is  regulated  chiefly  by  two  major  signalling  pathways: PI3K/Akt/mTOR  and Ras/MAPK/Mnk.  mTOR  directly  phosphorylates  the  4E-BPs  (eIF4E-binding  proteins),  which  are 
inhibitors of eIF4E, to relieve translational suppression, while Mnk phosphorylates eIF4E to stimulate translation.  Aberrations  in  these  pathways  result  in  dysregulated  eIF4E  activity,  which  engenders tumorigenesis and neurological disorders such as autism and Fragile-X syndrome.