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Related Concept Videos

Caspases01:24

Caspases

12.9K
Caspase, a family of cysteine proteases, serve as effectors in apoptosis. The ced3 gene in C.elegans was first identified to be involved in apoptosis. This gene encodes the ced-3 caspase that is similar to the interleukin-1-beta converting enzyme or ICE in mammals. In addition to apoptosis, caspases also function in the inflammatory response. Inflammatory caspases are essential in activating pro-inflammatory cytokines that recruit immune cells and block the replication of pathogens inside...
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MAPK Signaling Cascades01:07

MAPK Signaling Cascades

6.6K
Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
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Amplifying Signals via Enzymatic Cascade01:22

Amplifying Signals via Enzymatic Cascade

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When a ligand binds to a cell-surface receptor, the receptor's intracellular domain changes shape, which may either activate its enzyme function or allow its binding to other molecules. The initial signal is amplified by most signal transduction pathways. This means that a single ligand molecule can activate multiple molecules of a downstream target. Proteins that relay a signal are most commonly phosphorylated at one or more sites, activating or inactivating the protein. Kinases catalyze...
14.0K
The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

7.1K
Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
7.1K
Protein Kinases and Phosphatases02:54

Protein Kinases and Phosphatases

13.9K
Proteins undergo chemical modifications that trigger changes in the charge, structure, and conformation of the proteins. Phosphorylation, acetylation, glycosylation, nitrosylation, ubiquitination, lipidation, methylation, and proteolysis are various protein modifications that regulate protein activity. Such modifications are usually enzyme-driven.
Protein kinases
Many proteins in the cell are regulated by phosphorylation, the addition of a phosphate group. A family of enzymes called kinases...
13.9K
The Extrinsic Apoptotic Pathway01:17

The Extrinsic Apoptotic Pathway

6.8K
The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
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Engineered reactivity of a bacterial E1-like enzyme enables ATP-driven modification of protein and peptide C termini.

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Related Experiment Video

Updated: Oct 21, 2025

Lighting Up the Pathways to Caspase Activation Using Bimolecular Fluorescence Complementation
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Lighting Up the Pathways to Caspase Activation Using Bimolecular Fluorescence Complementation

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Kinases leave their mark on caspase substrates.

Amy M Weeks1

  • 1Department of Biochemistry, University of Wisconsin-Madison, Madison, WI 53706, U.S.A.

The Biochemical Journal
|September 7, 2021
PubMed
Summary

Phosphorylation near caspase cleavage sites can slow down, but not stop, substrate processing. This finding reveals complex regulation of apoptosis and potential therapeutic strategies.

Area of Science:

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Background:

  • Apoptosis is a regulated cell death process executed by caspases, a family of cysteine proteases.
  • Caspase activity involves a proteolytic cascade, cleaving substrates after aspartate residues.
  • Signaling crosstalk between caspase proteolysis and kinase phosphorylation integrates apoptotic pathway signals.

Purpose of the Study:

  • To investigate the impact of phosphorylation within caspase cleavage sites on substrate cleavage efficiency.
  • To understand how phosphorylation modulates the kinetics of caspase-mediated proteolysis.

Main Methods:

  • The study by Maluch et al. focused on analyzing the influence of phosphorylation on caspase substrate cleavage.
  • Quantitative analysis of substrate processing rates in the presence and absence of phosphorylation.
Keywords:
caspaseskinasespost translational modification

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Main Results:

  • Phosphorylation near the scissile bond generally inhibits caspase substrate cleavage.
  • Inhibition is typically rate-attenuating rather than absolute, allowing for continued, albeit slower, cleavage.
  • Favorable substrate features can overcome phosphorylation-induced inhibition in some instances.

Conclusions:

  • Phosphorylation of caspase substrates plays a nuanced role in regulating apoptosis.
  • These findings have implications for understanding caspase function and developing targeted therapeutics.