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How does caspases regulation play role in cell decisions? apoptosis and beyond

Negar Ghorbani1, Roham Yaghubi2, Jamshid Davoodi3

  • 1Department of Biochemistry, Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran.

Molecular and Cellular Biochemistry
|November 17, 2023
PubMed

Insights

Caspases, crucial for apoptosis and inflammation, also promote cell survival and cancer progression. Understanding regulators of caspase activity is vital for controlling their non-apoptotic functions and developing new therapies.

Area of Science:

  • Molecular Biology
  • Cellular Biology
  • Biochemistry

Background:

  • Caspases are cysteine proteases central to apoptosis and inflammation.
  • Emerging evidence reveals caspases also mediate pro-survival functions.
  • These non-apoptotic roles include cell proliferation, differentiation, and migration, impacting cancer metastasis and chemotherapy resistance.

Purpose of the Study:

  • To review mechanisms regulating caspase activity, focusing on their non-apoptotic functions.
  • To highlight the importance of controlling caspase activity for both mechanistic and clinical applications.
  • To discuss how caspases can be directed towards anti-apoptotic or non-apoptotic roles.

Main Methods:

  • Mini-review of existing literature on caspase regulation.
  • Discussion of various regulatory mechanisms impacting caspase function.
  • Focus on post-translational modifications (PTMs), isoforms, subcellular localization, transient activity, substrate availability, substrate selection, and interaction-mediated regulations.

Main Results:

  • Caspase activity is tightly regulated to maintain a threshold below apoptotic levels.
  • Post-translational modifications significantly influence caspase functions.
  • Multiple factors including isoforms, localization, and substrate interactions modulate caspase activity.

Conclusions:

  • Precise control of caspase activity is essential due to their dual pro-apoptotic and pro-survival roles.
  • Understanding these regulatory mechanisms is critical for therapeutic strategies targeting cancer and inflammatory diseases.
  • Further research into caspase regulation can unlock new avenues for clinical intervention.
Keywords:
ApoptosisApoptosis inhibitionCaspase regulatorsCaspasesNon-apoptotic function of caspases

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