Cyclin-dependent kinase-5/p35 phosphorylates Presenilin 1 to regulate carboxy-terminal fragment stability

Mol Cell Neurosci. 2002 May;20(1):13-20. doi: 10.1006/mcne.2002.1108.


Mutations in the Presenilin 1 gene are the cause of the majority of autosomal dominant familial forms of Alzheimer's disease. Presenilin 1 (PS1) is produced as a holoprotein but is then rapidly processed to amino- (N-PS1) and carboxy-terminal (C-PS1) fragments that are incorporated into stable high molecular mass complexes. The mechanisms that control PS1 cleavage and stability are not properly understood but sequences within C-PS1 have been shown to regulate both of these properties. Here we demonstrate that cyclin dependent kinase-5/p35 (cdk5/p35) phosphorylates PS1 on threonine(354) within C-PS1 both in vitro and in vivo. Threonine(354) phosphorylation functions to selectively stabilize C-PS1. Our results demonstrate that cdk5/p35 is a regulator of PS1 metabolism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / enzymology*
  • Alzheimer Disease / physiopathology
  • Animals
  • CHO Cells
  • Cell Membrane / enzymology*
  • Cerebral Cortex / enzymology*
  • Cerebral Cortex / physiopathology
  • Cricetinae
  • Cyclin-Dependent Kinase 5
  • Cyclin-Dependent Kinases / genetics
  • Cyclin-Dependent Kinases / metabolism*
  • Electrophoretic Mobility Shift Assay
  • Humans
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Neurons / enzymology*
  • Peptide Fragments / metabolism*
  • Phosphoprotein Phosphatases
  • Phosphorylation
  • Presenilin-1
  • Protein Structure, Tertiary / physiology
  • Rats
  • Transfection


  • Membrane Proteins
  • PSEN1 protein, human
  • Peptide Fragments
  • Presenilin-1
  • Cyclin-Dependent Kinase 5
  • CDK5 protein, human
  • Cdk5 protein, rat
  • Cyclin-Dependent Kinases
  • Phosphoprotein Phosphatases