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Fission yeast Cdc14-like phosphatase Flp1/Clp1 modulates the transcriptional response to oxidative stress

Juan A Canete1,2, Sonia Andrés1,2, Sofía Muñoz1,2

  • 1Instituto de Biología Molecular y Celular del Cáncer (IBMCC), Universidad de Salamanca-CSIC, Campus Miguel de Unamuno, 37007, Salamanca, Spain.

Scientific Reports
|September 6, 2023
PubMed

Insights

Fission yeast Flp1 phosphatase fine-tunes the oxidative stress response. Flp1 limits the Atf1/Pcr1 transcriptional response, with Flp1 ablation enhancing gene expression during cellular stress.

Area of Science:

  • Cellular Biology
  • Molecular Biology
  • Stress Response

Background:

  • Reactive oxygen species (ROS) cause cellular damage, leading to oxidative stress that impacts DNA stability and metabolism.
  • Stress-activated protein kinases (SAPKs) manage cellular responses to oxidative stress by regulating cell cycle progression and activating antioxidant mechanisms.
  • Fission yeast Flp1 (Clp1), a Cdc14-like phosphatase, is known for its roles in cell cycle regulation and replication stress response.

Purpose of the Study:

  • To investigate the role of Flp1 in the cellular oxidative stress response.
  • To elucidate the mechanism by which Flp1 modulates the transcriptional response to oxidative stress.

Main Methods:

  • Investigated Flp1's localization and function under oxidative stress conditions.
  • Analyzed the transcriptional response in wild-type and Flp1-deficient yeast strains.
  • Examined the interaction between Flp1 and the Atf1/Pcr1 complex, identifying Pcr1 as a direct substrate.

Main Results:

  • Flp1 undergoes phosphorylation-dependent nucleolar release in response to oxidative stress.
  • Flp1 deficiency leads to an amplified and prolonged transcriptional response to oxidative stress.
  • Flp1 interacts with the Atf1/Pcr1 complex, with Pcr1 being a direct substrate, suggesting Flp1's role in regulating this complex.

Conclusions:

  • Flp1 plays a critical role in fine-tuning the cellular oxidative stress response.
  • Flp1 modulates the oxidative stress response by limiting Atf1/Pcr1-mediated transcription.
  • Flp1's phosphorylation-dependent release from the nucleolus is a key event in adapting to oxidative stress.

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