Activation and cleavage of SASH1 by caspase-3 mediates an apoptotic response

Joshua T Burgess, Emma Bolderson, Mark N Adams, Anne-Marie Baird, Shu-Dong Zhang, Kathy A Gately, Kazuo Umezawa, Kenneth J O’Byrne, Derek J Richard

Research output: Contribution to journalArticle

6 Citations (Scopus)

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.
LanguageEnglish
Pagese2469
JournalCell Death and Disease
Volume7
Issue number11
DOIs
Publication statusPublished - 10 Nov 2016

Fingerprint

Caspase 3
Apoptosis
Neoplasms
src Homology Domains
Proteolysis
Chromatin
Cytoplasm
Cell Death
Transcription Factors
Amino Acids
Mutation
Growth
Proteins

Keywords

  • SASH1
  • caspase-3
  • apoptotic response

Cite this

Burgess, J. T., Bolderson, E., Adams, M. N., Baird, A-M., Zhang, S-D., Gately, K. A., ... Richard, D. J. (2016). Activation and cleavage of SASH1 by caspase-3 mediates an apoptotic response. Cell Death and Disease, 7(11), e2469. https://doi.org/10.1038/cddis.2016.364
Burgess, Joshua T ; Bolderson, Emma ; Adams, Mark N ; Baird, Anne-Marie ; Zhang, Shu-Dong ; Gately, Kathy A ; Umezawa, Kazuo ; O’Byrne, Kenneth J ; Richard, Derek J. / Activation and cleavage of SASH1 by caspase-3 mediates an apoptotic response. In: Cell Death and Disease. 2016 ; Vol. 7, No. 11. pp. e2469.
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Burgess, JT, Bolderson, E, Adams, MN, Baird, A-M, Zhang, S-D, Gately, KA, Umezawa, K, O’Byrne, KJ & Richard, DJ 2016, 'Activation and cleavage of SASH1 by caspase-3 mediates an apoptotic response', Cell Death and Disease, vol. 7, no. 11, pp. e2469. https://doi.org/10.1038/cddis.2016.364

Activation and cleavage of SASH1 by caspase-3 mediates an apoptotic response. / Burgess, Joshua T; Bolderson, Emma; Adams, Mark N; Baird, Anne-Marie; Zhang, Shu-Dong; Gately, Kathy A; Umezawa, Kazuo; O’Byrne, Kenneth J; Richard, Derek J.

In: Cell Death and Disease, Vol. 7, No. 11, 10.11.2016, p. e2469.

Research output: Contribution to journalArticle

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AU - Bolderson, Emma

AU - Adams, Mark N

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AU - Gately, Kathy A

AU - Umezawa, Kazuo

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AU - Richard, Derek J

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