Related Experiment Video

Updated: Sep 26, 2026

Lighting Up the Pathways to Caspase Activation Using Bimolecular Fluorescence Complementation
08:47

Lighting Up the Pathways to Caspase Activation Using Bimolecular Fluorescence Complementation

Published on: March 5, 2018

Caspase-mediated cleavage of the U snRNP-associated Sm-F protein during apoptosis

K C R Malmegrim de Farias1, X Saelens, G J M Pruijn

  • 1Department of Biochemistry, Nijmegen Center for Molecular Life Sciences, University of Nijmegen, NL-6500 HB, Nijmegen, The Netherlands.

Cell Death and Differentiation
|May 3, 2003
PubMed

Insights

Dying cells release modified autoantigens, potentially causing autoimmunity. Researchers found that the Sm-F protein in apoptotic cells is cleaved by caspases, creating a fragment recognized by lupus patient autoantibodies.

Area of Science:

  • Immunology
  • Molecular Biology
  • Cell Biology

Background:

  • Systemic autoimmunity may arise from modified autoantigens in dying cells.
  • Anti-Sm autoantibodies, found in systemic lupus erythematosus (SLE) patients, target spliceosomal Sm proteins.

Purpose of the Study:

  • To investigate the impact of apoptosis on Sm proteins.
  • To determine if Sm protein modification during apoptosis contributes to autoantigen generation.

Main Methods:

  • Studied the effects of apoptosis on Sm proteins using biochemical assays.
  • Identified the specific Sm protein cleaved and characterized the cleavage site.
  • Utilized caspase inhibitors to determine the enzymes involved in Sm-F cleavage.
  • Generated and analyzed a C-terminally truncated Sm-F mutant in vitro.

Main Results:

  • The Sm-F protein undergoes proteolytic cleavage during apoptosis.
  • Cleavage generates a 9-kDa fragment that remains associated with U snRNP complexes.
  • Sm-F cleavage is dependent on caspase activation, with evidence implicating caspases beyond caspase-8.
  • A C-terminally truncated Sm-F mutant mimics the apoptotic form and is recognized by anti-Sm autoantibodies from SLE patients.

Conclusions:

  • Apoptosis modifies Sm-F protein through caspase-dependent cleavage.
  • This cleavage generates a novel autoantigenic form of Sm-F.
  • The modified Sm-F protein may play a role in the pathogenesis of systemic lupus erythematosus.

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

Measuring Composition of CD95 Death-Inducing Signaling Complex and Processing of Procaspase-8 in this Complex07:17

Measuring Composition of CD95 Death-Inducing Signaling Complex and Processing of Procaspase-8 in this Complex

Published on: August 2, 2021

Related Concept Videos

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...
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...
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.
RNA Splicing01:32

RNA Splicing

Splicing is the process by which eukaryotic RNA is edited before its translation into protein. The RNA strand transcribed from eukaryotic DNA is called the primary transcript. The primary transcripts that become mRNAs are called precursor messenger RNAs (pre-mRNAs). Eukaryotic pre-mRNA contains alternating sequences of exons and introns. Exons are nucleotide sequences that code for proteins, whereas introns are the non-coding regions. In RNA splicing, introns are removed and exons are bonded...
Nonsense-mediated mRNA Decay02:27

Nonsense-mediated mRNA Decay

The Upf proteins that carry out nonsense-mediated decay (NMD) are found in all eukaryotic organisms, including humans. Each protein has an individual role, but they need to work in collaboration. Upf1 is an ATP-dependent RNA helicase that unwinds the RNA helix. Because Upf1 can unwind any RNA, Upf2 and Upf3 are required to help Upf1 discriminate between nonsense and normal mRNAs.
Usually, Upf3 binds to an Exon Junction Complex (EJC) at mRNA splice sites. If a ribosome fully translates the mRNA,...