Inhibition of p-mTOR represses PS1 transcription by reducing p-JNK

Hriday K. Das, Silahis S. Hontiveros

Research output: Contribution to journalArticlepeer-review

1 Scopus citations


Presenilin-1 (PS1) is the catalytic subunit of gamma-secretase. PS1 cleaves beta-amyloid precursor protein (APP) to produce Abeta peptide and Notch 1 receptor to release Notch intracellular domain (NICD) in the cytoplasm. We have previously shown that rapamycin inhibits p-mTOR to repress PS1 transcription and Notch 1-signaling. But the exact mechanism by which rapamycin inhibits PS1 transcription is not known. We have also published that inhibition of basal activity of c-jun-NH2-terminal kinase (JNK) with JNK-specific inhibitor SP600125 represses PS1 transcription by reducing p-JNK and via p53 dependent mechanism. We now report that rapamycin inhibits the phosphorylation of both mTOR (p-mTOR) and JNK (p-JNK). It appears that rapamycin represses PS1 transcription by inhibiting the expression of p-JNK in SK-N-SH cells under non-stressed condition. Consequently, one of the mechanisms of inhibition of PS1 transcription by rapamycin is similar to the mechanism of repression of PS1 transcription by JNK-specific inhibitor SP600125. We also report that JNK-inhibitor SP6000125 decreases both p-JNK and p-mTOR protein levels. These results suggest that JNK and mTOR may potentially activate each other by mutual phosphorylation.

Original languageEnglish
Pages (from-to)1297-1304
Number of pages8
JournalFrontiers in Bioscience - Landmark
Issue number7
StatePublished - 1 Mar 2020


  • Alzheimer's disease
  • MTOR signaling
  • P-JNK
  • PS1


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