Endoplasmic reticulum stress induces G2 cell-cycle arrest via mRNA translation of the p53 isoform p53/47.
p53 downstream pathways control G1 and G2 cell-cycle arrest, DNA repair, or apoptosis. However, it is still not clear how cells differentiate the cell-biological outcome of p53 activation in response to different types of stresses. The p53/47 isoform lacks the first 39 amino acids of full-length p53 including the Mdm2 binding site and the first trans-activation domain, and tetramers including p53/47 exhibit altered activity and biochemical properties. Here we show that endoplasmic reticulum stress promotes PERK-dependent induction of p53/47 mRNA translation and p53/47 homo-oligomerization. p53/47 induces 14-3-3sigma and G2 arrest but does not affect G1 progression. This is contrary to p53FL, which promotes G1 arrest but has no effect on the G2. These results show a unique role for p53/47 in the p53 pathway and illustrate how a cellular stress leads to a defined cell-biological outcome through expression of a p53 isoform.
Bourougaa
Karima
K
INSERM Unité 716, Institut de Génétique Moléculaire, Université Paris 7, Hôpital St. Louis, 27 Rue Juliette Dodu, 75010 Paris, France.
Naski
Nadia
N
Boularan
Cedric
C
Mlynarczyk
Coraline
C
Candeias
Marco M
MM
Marullo
Stefano
S
Fåhraeus
Robin
R
D048948:14-3-3 Proteins; D017209:Apoptosis / Q000502:physiology; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D005092:Exonucleases / Q000235:genetics / Q000378:metabolism; D005095:Exoribonucleases; D016195:G2 Phase / Q000502:physiology*; D006801:Humans; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D014176:Protein Biosynthesis; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D013312:Stress, Physiological; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*; D019892:eIF-2 Kinase / Q000235:genetics / Q000378:metabolism
D048948:14-3-3 Proteins; D014408:Biomarkers, Tumor; D005092:Exonucleases; D005095:Exoribonucleases; D009363:Neoplasm Proteins; D020033:Protein Isoforms; D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53; D019892:eIF-2 Kinase; C413442:SFN protein, human