Related Experiment Videos
Many cuts to ruin: a comprehensive update of caspase substrates
U Fischer1, R U Jänicke, K Schulze-Osthoff
1Institute of Molecular Medicine, University of Düsseldorf, Germany.
Abstract:
Apoptotic cell death is executed by the caspase-mediated cleavage of various vital proteins. Elucidating the consequences of this endoproteolytic cleavage is crucial for our understanding of cell death and other biological processes. Many caspase substrates are just cleaved as bystanders, because they happen to contain a caspase cleavage site in their sequence. Several targets, however, have a discrete function in propagation of the cell death process. Many structural and regulatory proteins are inactivated by caspases, while other substrates can be activated. In most cases, the consequences of this gain-of-function are poorly understood. Caspase substrates can regulate the key morphological changes in apoptosis. Several caspase substrates also act as transducers and amplifiers that determine the apoptotic threshold and cell fate. This review summarizes the known caspase substrates comprising a bewildering list of more than 280 different proteins. We highlight some recent aspects inferred by the cleavage of certain proteins in apoptosis. We also discuss emerging themes of caspase cleavage in other forms of cell death and, in particular, in apparently unrelated processes, such as cell cycle regulation and cellular differentiation.
Insights
Caspase cleavage of proteins drives apoptotic cell death. This review details over 280 caspase substrates, exploring their roles in cell death, cell cycle, and differentiation.
Area of Science:
- Molecular Biology
- Cell Biology
- Biochemistry
Background:
- Apoptotic cell death involves caspase-mediated cleavage of vital proteins.
- Understanding these cleavage events is crucial for cell death research.
- Caspase substrates can be inactivated or activated, with poorly understood functional consequences.
Purpose of the Study:
- To review known caspase substrates and their roles in apoptosis.
- To highlight recent findings on protein cleavage during apoptosis.
- To discuss caspase cleavage in other cell death forms and processes like cell cycle regulation and differentiation.
Main Methods:
- Literature review of caspase substrates.
- Analysis of functional consequences of caspase cleavage.
- Synthesis of information on caspase activity in diverse biological processes.
Main Results:
- Over 280 caspase substrates have been identified.
- Caspase substrates regulate key apoptotic morphological changes.
- Some substrates act as transducers and amplifiers, influencing apoptotic threshold and cell fate.
Conclusions:
- Caspase cleavage is central to apoptosis execution and regulation.
- Emerging roles of caspase cleavage extend to cell cycle and differentiation.
- Further research is needed to fully elucidate the functional outcomes of caspase substrate activation.