p53 is regulated by and regulates members of the gamma-secretase complex.
Amyloid beta-peptides is the generic term for a set of hydrophobic peptides that accumulate in Alzheimer's disease (AD)-affected brains. These amyloid-beta peptide fragments are mainly generated by an enzymatic machinery referred to as gamma-secretase complex that is built up by the association of four distinct proteins, namely presenilin 1 (PS1) or PS2, nicastrin, Aph-1 and Pen-2. AD is also characterized by exacerbated cell death that appears linked to the tumor suppressor p53. Interestingly, all members of the gamma-secretase complex control p53-dependent cell death. On the other hand, p53 appears to be able to regulate directly or indirectly the expression and transcription of PS1, PS2 and Pen-2. This review will focus on the functional cross-talk between the members of the gamma-secretase complex and p53 and will discuss the putative implication of this oncogene in AD pathology.
Checler
Frédéric
F
Institut de Pharmacologie Moléculaire et Cellulaire et Institut de NeuroMédecine Moléculaire, UMR6097 CNRS/UNSA, Valbonne, France. checler@ipmc.cnrs.fr
Dunys
Julie
J
Pardossi-Piquard
Raphaelle
R
Alves da Costa
Cristine
C
D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism*; D053829:Amyloid Precursor Protein Secretases / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D016923:Cell Death / Q000235:genetics; D002461:Cell Line, Transformed; D005786:Gene Expression Regulation / Q000235:genetics; D006801:Humans; D051379:Mice; D008954:Models, Biological; D053764:Presenilin-1 / Q000235:genetics / Q000378:metabolism; D053766:Presenilin-2 / Q000235:genetics / Q000378:metabolism; D014162:Transfection / Q000379:methods; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
C508861:PSEN2 protein, human; D053764:Presenilin-1; D053766:Presenilin-2; D016159:Tumor Suppressor Protein p53; D053829:Amyloid Precursor Protein Secretases