Related Experiment Video

Updated: Aug 6, 2026

LPS and ATP-induced Death of PMA-differentiated THP-1 Macrophages and its Validation
06:12

LPS and ATP-induced Death of PMA-differentiated THP-1 Macrophages and its Validation

Published on: May 3, 2024

The MPAC domain is a novel mitotically regulated domain, removed by apoptotic protease cleavage during cell death

Sarah Spinette1, James A Mahoney, Antony Rosen

  • 1Department of Medicine, Division of Rheumatology, Johns Hopkins University, Baltimore, MD, USA.

Biochemical and Biophysical Research Communications
|July 28, 2006
PubMed

Insights

Apoptotic proteases like caspases and granzyme B cleave similar substrates. Researchers discovered a novel MPAC domain in Ufd2a and polyA polymerase (PAP) regulated by phosphorylation and cleavage.

Area of Science:

  • Molecular Biology
  • Biochemistry
  • Evolutionary Biology

Background:

  • Apoptotic proteases, including caspases and granzyme B, share substrate specificity despite independent evolutionary origins.
  • Many substrates of these proteases are also regulated during the cell cycle.

Purpose of the Study:

  • To identify novel domains regulated by both mitotic phosphorylation and apoptotic cleavage.
  • To investigate the evolutionary relationship between apoptotic proteases and their substrates.

Main Methods:

  • Bioinformatic analysis to identify conserved domains.
  • Biochemical assays to study protein regulation (phosphorylation and cleavage).

Main Results:

  • Identification of a novel Mitotically Phosphorylated, Apoptotically Cleaved (MPAC) domain at the N-terminus of Ufd2a.
  • Discovery of a corresponding domain in polyA polymerase (PAP) regulated by mitotic phosphorylation and apoptotic cleavage.
  • The apoptotic cleavage site in PAP acts as a novel connector between regulatory and functional domains.

Conclusions:

  • The MPAC domain and its counterpart in PAP provide new insights into dual regulation by mitosis and apoptosis.
  • The positioning of the cleavage site suggests a role in the evolution of apoptotic protease function.
  • Findings illuminate the structural and functional evolution of specific proteases.

More Related Videos

Evaluation of Caspase Activation to Assess Innate Immune Cell Death10:23

Evaluation of Caspase Activation to Assess Innate Immune Cell Death

Published on: January 20, 2023

Detection of Mitochondria Membrane Potential to Study CLIC4 Knockdown-induced HN4 Cell Apoptosis In Vitro13:20

Detection of Mitochondria Membrane Potential to Study CLIC4 Knockdown-induced HN4 Cell Apoptosis In Vitro

Published on: July 17, 2018

Related Concept Videos

The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

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...
Caspases01:24

Caspases

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 cells.
The Extrinsic Apoptotic Pathway01:17

The Extrinsic Apoptotic Pathway

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...
Anaphase Promoting Complex00:50

Anaphase Promoting Complex

The stepwise destruction of specific proteins is necessary for the progression and completion of the cell cycle. Such proteins are ubiquitinated by ubiquitin ligases and then subsequently destroyed by the proteasome. The SCF (Skp1/Cullin/F-box) and the anaphase-promoting complex (APC) are two important ubiquitin ligases involved in cell cycle progression. While SCF is active throughout the cell cycle, APC gets activated during metaphase to anaphase transition. Cdc20 or Cdh1 binds to APC and...
Apoptosis01:30

Apoptosis

Apoptosis is a combination of two Greek words, 'apo' and 'ptosis,' meaning separation and falling off, respectively. Hippocrates used this word to describe gangrene, which was caused due to bandaging of fractured bones. Apoptosis was distinguished from necrosis in 1970 when John Kerr reported observations of morphological changes occurring during apoptosis. During one experiment, he observed that the disruption of blood supply to the liver tissue resulted in a size reduction of the tissue.
Phagocytosis of Apoptotic Cells01:17

Phagocytosis of Apoptotic Cells

Cells undergoing apoptosis form apoptotic bodies that must be removed immediately to prevent inflammation, autoimmune diseases, and necrosis. Phagocytosis is carried out by professional phagocytes such as macrophages or  immature dendritic cells. Non-professional phagocytes such as  epithelial cells and fibroblasts also take part in this process; however, they are not as effective as professional phagocytes. 
Normal cells contain receptors that prevent them from being recognized by phagocytes.