Phosphorylation of nicastrin by SGK1 leads to its degradation through lysosomal and proteasomal pathways

Jung Soon Mo, Ji Hye Yoon, Ji Ae Hong, Mi Yeon Kim, Eun Jung Ann, Ji Seon Ahn, Su Man Kim, Hyeong Jin Baek, Florian Lang, Eui Ju Choi, Hee Sae Park

Research output: Contribution to journalArticlepeer-review

13 Citations (Scopus)


The gamma-secretase complex is involved in the intramembranous proteolysis of a variety of substrates, including the amyloid precursor protein and the Notch receptor. Nicastrin (NCT) is an essential component of the gamma-secretase complex and functions as a receptor for gamma-secretase substrates. In this study, we determined that serum- and glucocorticoid-induced protein kinase 1 (SGK1) markedly reduced the protein stability of NCT. The SGK1 kinase activity was decisive for NCT degradation and endogenous SGK1 inhibited gamma-secretase activity. SGK1 downregulates NCT protein levels via proteasomal and lysosomal pathways. Furthermore, SGK1 directly bound to and phosphorylated NCT on Ser437, thereby promoting protein degradation. Collectively, our findings indicate that SGK1 is a gamma-secretase regulator presumably effective through phosphorylation and degradation of NCT.

Original languageEnglish
Article numbere37111
JournalPloS one
Issue number5
Publication statusPublished - 2012 May 10

ASJC Scopus subject areas

  • General Biochemistry,Genetics and Molecular Biology
  • General Agricultural and Biological Sciences
  • General


Dive into the research topics of 'Phosphorylation of nicastrin by SGK1 leads to its degradation through lysosomal and proteasomal pathways'. Together they form a unique fingerprint.

Cite this