Review on AKT1S1, with data on DNA\/RNA, on the protein encoded and where the gene is implicated.
Nucleolar stress response
Nuclear AKT1S1 binds to the ribosomal protein L11 (RPL11) (Havel et al., 2014). This interaction is dependent on the phosphorylation of Ser221 and Thr246 within AKT1S1 (Havel et al., 2014). RPL11 has been linked to the inhibition of the E3 ubiquitin ligase HDM2. This results in increased p53 protein stability and activation of the nucleolar stress response pathway, which is defined as the activation of a specific transcriptional program resulting in cell cycle arrest, apoptosis or senescence. The activation of this pathway is prevented when RPL11 is bound to AKT1S1 (Havel et al., 2014).
Akt1S1 protects neurons against cell death following spinal cord injury (Saito et al., 2004). Overexpression of AKT1S1 in rats reduces infarct size following cerebral ischemia (Saito et al., 2006; Yu et al., 2008).
Proteasome activity and insulin sensitivity
The silencing of AKT1S1 promotes the degradation of insulin receptor substrate 1 (IRS1) in skeletal muscle through activation of the proteasome (Wiza et al., 2013a). As a consequence, the insulin-mediated activation of IRS1/Akt signaling pathway regulating glucose uptake is impaired (Wiza et al., 2013a). Conversely, overexpression of AKT1S1 inhibits proteasome activation and increases IRS1 stability (Wiza et al., 2014). This results in increased insulin sensitivity even under conditions of insulin resistance. Overexpression of AKT1S1 improves insulin signaling via the IRS1/Akt-axis in the heart and liver of a high-fat diet mouse model for insulin resistance (Völkers et al., 2014).
Claudia Wiza ; Emmani BM Nascimento ; D Margriet Ouwens
AKT1S1 (AKT1 substrate 1 (proline-rich))
Atlas Genet Cytogenet Oncol Haematol. 2014-11-01
Online version: http://atlasgeneticsoncology.org/gene/44289/akt1s1