Studying p53 family proteins in yeast: Induction of autophagic cell death and modulation by interactors and small molecules

• Type: Article in International Scientific Journal
• Date: 2015

Authors

Mariana Leao (Author) Other; Sara Gomes (Author) Other; Claudia Bessa (Author) Other; Joana Soares (Author) Other; Liliana Raimundo (Author) Other; Paola Monti (Author) Other; Gilberto Fronza (Author) Other; Clara Pereira (Author) Other; Lucilia Saraiva (Author) FFUP

Journal

Title: Experimental Cell Research

Vol. 330

Pages: 164-177

ISSN: 0014-4827

Publisher: Elsevier

Indexing

ISI Web of Knowledge - 12 Citations

Scopus - 14 Citations

Scientific classification

FOS: Medical and Health sciences > Clinical medicine

Other information

Authenticus ID: P-00A-1ZY

DOI: 10.1016/j.yexcr.2014.09.028

Abstract (EN): 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 were analyzed. When expressed in yeast, wild-type p53, TAp63, ANp63 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, ANp63 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.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 14