Document Detail

Studying p53 family proteins in yeast: Induction of autophagic cell death and modulation by interactors and small molecules.
MedLine Citation:
PMID:  25265062     Owner:  NLM     Status:  Publisher    
In this work, the yeast Saccharomyces cerevisiae was used to individually study human p53, p63 (full length and truncated forms) and p73. Using this cell system, the effect of these proteins on cell proliferation and death, and the influence of MDM2 and MDMX on their activities was analysed. When expressed in yeast, wild-type p53, TAp63, ΔNp63 and TAp73 induced growth inhibition associated with S-phase cell cycle arrest. This growth inhibition was accompanied by reactive oxygen species production and autophagic cell death. Furthermore, they stimulated rapamycin-induced autophagy. On the contrary, none of the tested p53 family members induced apoptosis either per se or after apoptotic stimuli. As previously reported for p53, also TAp63, ΔNp63 and TAp73 increased actin expression levels and its depolarization, suggesting that ACT1 is also a p63 and p73 putative yeast target gene. Additionally, MDM2 and MDMX inhibited the activity of all tested p53 family members in yeast, although the effect was weaker on TAp63. Moreover, Nutlin-3a and SJ-172550 were identified as potential inhibitors of the p73 interaction with MDM2 and MDMX, respectively. Altogether, the yeast-based assays herein developed can be envisaged as a simplified cell system to study the involvement of p53 family members in autophagy, the modulation of their activities by specific interactors (MDM2 and MDMX), and the potential of new small molecules to modulate these interactions.
Mariana Leão; Sara Gomes; Cláudia Bessa; Joana Soares; Liliana Raimundo; Paola Monti; Gilberto Fronza; Clara Pereira; Lucília Saraiva
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-9-26
Journal Detail:
Title:  Experimental cell research     Volume:  -     ISSN:  1090-2422     ISO Abbreviation:  Exp. Cell Res.     Publication Date:  2014 Sep 
Date Detail:
Created Date:  2014-9-29     Completed Date:  -     Revised Date:  2014-9-30    
Medline Journal Info:
Nlm Unique ID:  0373226     Medline TA:  Exp Cell Res     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2014. Published by Elsevier Inc.
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