SIAH1 ubiquitin ligase mediates ubiquitination and degradation of Akt3 in neural development.Akt signaling is an important regulator of neural development, but the distinctive function of Akt isoforms in brain development presents a challenge.  Here we show Siah1 as an ubiquitin ligase that preferentially interacts with Akt3 and facilitates ubiquitination and degradation of Akt3.  Akt3 is enriched in the axonal shaft and branches but not growth cone tips, where Siah1 is prominently present.  Depletion of Siah1 enhanced Akt3 levels in the soma and axonal tips, eliciting multiple branching.  Brain-specific somatic mutation in Akt3-E17K escapes from Siah1-mediated degradation and causes improper neural development with dysmorphic neurons.  Remarkably, coexpression of Siah1 with Akt3-WT restricted disorganization of neural development is caused by Akt3 overexpression, whereas forced expression of Siah1 with the Akt3-E17K mutant fails to cope with malformation of neural development.  These findings demonstrate that Siah1 limits Akt3 turnover during brain development and that this event is essential for normal organization of the neural network.
SIAH1
SIAH1 ubiquitin ligase mediates ubiquitination and degradation of Akt3 in neural development.Akt signaling is an important regulator of neural development, but the distinctive function of Akt isoforms in brain development presents a challenge. 
SIAH1 ubiquitin ligase
SIAH1 ubiquitin ligase mediates ubiquitination and degradation of Akt3 in neural development.Akt signaling is an important regulator of neural development, but the distinctive function of Akt isoforms in brain development presents a challenge. 
SIAH1 ubiquitin ligase
SIAH1 ubiquitin ligase mediates ubiquitination and degradation of Akt3 in neural development.Akt signaling is an important regulator of neural development, but the distinctive function of Akt isoforms in brain development presents a challenge. 
SIAH1 ubiquitin ligase
SIAH1 ubiquitin ligase mediates ubiquitination and degradation of Akt3 in neural development.Akt signaling is an important regulator of neural development, but the distinctive function of Akt isoforms in brain development presents a challenge. 
SIAH1 ubiquitin ligase
SIAH1 ubiquitin ligase mediates ubiquitination and degradation of Akt3 in neural development.Akt signaling is an important regulator of neural development, but the distinctive function of Akt isoforms in brain development presents a challenge. 
SIAH1 ubiquitin ligase