Related Experiment Video
Updated: Mar 12, 2026
Lighting Up the Pathways to Caspase Activation Using Bimolecular Fluorescence Complementation
Published on: March 5, 2018
Activation and cleavage of SASH1 by caspase-3 mediates an apoptotic response
Joshua T Burgess1, Emma Bolderson1,2, Mark N Adams1
1Cancer and Ageing Program, Institute of Health and Biomedical Innovation at the Translational Research Institute (TRI), Queensland University of Technology (QUT) and Princess Alexandra Hospital, Level 6, Translational Research Institute, Brisbane, QLD, Australia.
Abstract:
Apoptosis is a highly regulated cellular process that functions to remove undesired cells from multicellular organisms. This pathway is often disrupted in cancer, providing tumours with a mechanism to avoid cell death and promote growth and survival. The putative tumour suppressor, SASH1 (SAM and SH3 domain containing protein 1), has been previously implicated in the regulation of apoptosis; however, the molecular role of SASH1 in this process is still unclear. In this study, we demonstrate that SASH1 is cleaved by caspase-3 following UVC-induced apoptosis. Proteolysis of SASH1 enables the C-terminal fragment to translocate from the cytoplasm to the nucleus where it associates with chromatin. The overexpression of wild-type SASH1 or a cleaved form of SASH1 representing amino acids 231-1247 leads to an increase in apoptosis. Conversely, mutation of the SASH1 cleavage site inhibits nuclear translocation and prevents the initiation of apoptosis. SASH1 cleavage is also required for the efficient translocation of the transcription factor nuclear factor-κB (NF-κB) to the nucleus. The use of the NF-κB inhibitor DHMEQ demonstrated that the effect of SASH1 on apoptosis was dependent on NF-κB, indicating a codependence between SASH1 and NF-κB for this process.
Insights
The tumor suppressor SASH1 (SAM and SH3 domain containing protein 1) is cleaved during UVC-induced apoptosis, translocating to the nucleus to promote cell death. This cleavage is essential for SASH1
Area of Science:
- Cellular Biology
- Molecular Oncology
- Biochemistry
Background:
- Apoptosis is a crucial regulated cellular process for removing unwanted cells.
- Dysregulation of apoptosis is a hallmark of cancer, promoting tumor growth and survival.
- The tumor suppressor SASH1's role in apoptosis regulation is not fully understood.
Purpose of the Study:
- To elucidate the molecular mechanism of SASH1 in apoptosis.
- To investigate the role of SASH1 cleavage in cellular processes.
- To determine the relationship between SASH1 and nuclear factor-κB (NF-κB) in apoptosis.
Main Methods:
- Induction of apoptosis using UVC irradiation.
- Analysis of SASH1 cleavage by caspase-3.
- Tracking of SASH1 C-terminal fragment translocation using microscopy.
- Overexpression of wild-type and mutated SASH1.
- Inhibition of nuclear factor-κB (NF-κB) signaling pathway.
Main Results:
- SASH1 is cleaved by caspase-3 during UVC-induced apoptosis.
- The cleaved SASH1 C-terminal fragment translocates to the nucleus and associates with chromatin.
- Overexpression of SASH1 or its cleaved form enhances apoptosis.
- Mutation of the SASH1 cleavage site abrogates nuclear translocation and apoptosis initiation.
- SASH1 cleavage is necessary for efficient nuclear translocation of NF-κB.
- SASH1's pro-apoptotic effect is dependent on NF-κB signaling.
Conclusions:
- SASH1 cleavage by caspase-3 is a critical event in UVC-induced apoptosis.
- Nuclear translocation of cleaved SASH1 promotes apoptosis.
- SASH1 and NF-κB signaling pathways are codependent for SASH1-mediated apoptosis.
Related Concept Videos
01:24Caspases
01:31The Intrinsic Apoptotic Pathway
01:17The Extrinsic Apoptotic Pathway
01:30Apoptosis
01:17Phagocytosis of Apoptotic Cells
Normal cells contain receptors that prevent them from being recognized...
01:07MAPK Signaling Cascades