Page 6 - F. Cell biology

[F. Cell biology-3]

Novel degradation mechanism of c-Fos by AKT2-mediated

autophagy pathway

Wooram Choi¹˙#, Deok Jeong¹˙#, Han Gyung Kim¹, Yo Han Hong¹, Chaoran Song¹, Long You¹, Jieun Oh¹,
Jae Youl Cho¹˙*

¹Integrative Biotechnology, SungKyunKwan University, Suwon 16419, Korea

Autophagy is an important autolysis process that responds to a variety of stresses and maintains intracellular balance,

contributing to cell homeostasis. Although AKT is an important signaling protein in the cell pathway, its role is not
fully understood in autophagy. We found that treatment with the protein phosphatase inhibitor pervanadate in

RAW264.7 cells induced by LPS significantly reduced c-Fos levels. We used protein degradation inhibitors such as
MG132, AICAR and 3-MA to demonstrate regulatory mechanisms. Surprisingly, c-Fos levels were restored only by

lysosomal degradation inhibitors. We have found, interestingly, that c-Fos degradation is restored by reduced AKT
activity during exposure of the PI3K inhibitor LY294002. In addition, AKT2 alone was involved in c-Fos degradation

according to AKT2-overexpression conditions and treatment of AKT2-specific inhibitors. In addition, c-Fos
degradation was restored by inhibition of autophagy such as 3-MA, chloroquine and shATG5 knockdown. In addition,

the AKT2 kinase domain has been found to be essential for c-Fos degradation through immunoprecipitation and
protein mutation analysis. Therefore, our data strongly suggest that AKT2 can induce autophagy pathway and that

it can perform important enzymes in c-Fos degradation.