Proteomic analyses reveal that Sky1 modulates apoptosis and mitophagy in Saccharomyces cerevisiae cells exposed to cisplatin

Int J Mol Sci. 2014 Jul 15;15(7):12573-90. doi: 10.3390/ijms150712573.

Abstract

Sky1 is the only member of the SR (Serine-Arginine) protein kinase family in Saccharomyces cerevisiae. When yeast cells are treated with the anti-cancer drug cisplatin, Sky1 kinase activity is necessary to produce the cytotoxic effect. In this study, proteome changes in response to this drug and/or SKY1 deletion have been evaluated in order to understand the role of Sky1 in the response of yeast cells to cisplatin. Results reveal differential expression of proteins previously related to the oxidative stress response, DNA damage, apoptosis and mitophagy. With these precedents, the role of Sky1 in apoptosis, necrosis and mitophagy has been evaluated by flow-cytometry, fluorescence microscopy, biosensors and fluorescence techniques. After cisplatin treatment, an apoptotic-like process diminishes in the ∆sky1 strain in comparison to the wild-type. The treatment does not affect mitophagy in the wild-type strain, while an increase is observed in the ∆sky1 strain. The increased resistance to cisplatin observed in the ∆sky1 strain may be attributable to a decrease of apoptosis and an increase of mitophagy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Apoptosis*
  • Cisplatin / pharmacology*
  • DNA Damage
  • Drug Resistance, Neoplasm / genetics
  • Mitophagy*
  • Oxidative Stress
  • Protein Serine-Threonine Kinases / genetics
  • Protein Serine-Threonine Kinases / metabolism*
  • Proteome / genetics
  • Proteome / metabolism
  • Saccharomyces cerevisiae / drug effects
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism*
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism*

Substances

  • Antineoplastic Agents
  • Proteome
  • Saccharomyces cerevisiae Proteins
  • SKY1 protein, S cerevisiae
  • Protein Serine-Threonine Kinases
  • Cisplatin