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Caspase-2 Substrates: To Apoptosis, Cell Cycle Control, and Beyond

Alexandra N Brown-Suedel1,2, Lisa Bouchier-Hayes1,2

  • 1Hematology-Oncology Section, Department of Pediatrics, Department of Molecular Cell Biology, Baylor College of Medicine, Houston, TX, United States.

Frontiers in Cell and Developmental Biology
|January 11, 2021
PubMed

Insights

Caspase-2, a tumor suppressor protein, has unclear functions in apoptosis and cell cycle regulation. This review explores its substrates to understand its tumor-suppressing mechanism.

Area of Science:

  • Molecular Biology
  • Cellular Biology
  • Cancer Research

Background:

  • Caspase-2 is a member of the caspase protein family involved in apoptosis and inflammation.
  • It is recognized as a tumor suppressor, but its precise regulatory mechanisms remain largely unknown.
  • Conflicting evidence exists regarding its role in apoptosis, leading to its classification as an "orphan" caspase.

Purpose of the Study:

  • To review the known substrates of caspase-2.
  • To elucidate the functional relevance of these substrates to caspase-2's tumor suppressor activity.
  • To clarify the opposing functions of caspase-2 in apoptosis, cell cycle, and genomic stability.

Main Methods:

  • Literature review of existing studies on caspase-2.
  • Analysis of reported caspase-2 substrates.
  • Functional analysis of substrates in relation to tumor suppression.

Main Results:

  • Caspase-2 exhibits both apoptotic and non-apoptotic functions, including roles in cell cycle regulation and genomic instability.
  • The proteolytic cleavage of specific cellular substrates by caspase-2 is proposed as its primary mechanism of action.
  • Identified substrates play critical roles in cellular processes relevant to tumor suppression.

Conclusions:

  • Caspase-2's tumor suppressor function is mediated through the proteolytic activity on its substrates.
  • Understanding these substrates is key to deciphering the complex, dual role of caspase-2 in cellular regulation.
  • Further research into caspase-2 substrates will illuminate its therapeutic potential in cancer.
Keywords:
BIDMDM2PIDDRaiddapoptosiscaspase-2cell cycletumor suppressor

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