TRIM16 overexpression induces apoptosis through activation of caspase-2 in cancer cells

Patrick Y. Kim, Aldwin Suryo Rahmanto, Owen Tan, Murray D. Norris, Michelle Haber, Glenn M. Marshall*, Belamy B. Cheung

*Corresponding author for this work

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Abstract

TRIM16 exhibits tumour suppressor functions by interacting with cytoplasmic vimentin and nuclear E2F1 proteins in neuroblastoma and squamous cell carcinoma cells, reducing cell migration and replication. Reduced TRIM16 expression in a range of human primary malignant tissues correlates with increased malignant potential. TRIM16 also induces apoptosis in breast and lung cancer cells, by unknown mechanisms. Here we show that overexpression of TRIM16 induces apoptosis in human breast cancer (MCF7) and neuroblastoma (BE(2)-C) cells, but not in non-malignant HEK293 cells. TRIM16 increased procaspase-2 protein levels in MCF7 and induced caspase-2 activity in both MCF7 and BE(2)-C cells. We show that TRIM16 and caspase-2 proteins directly interact in both MCF7 and BE(2)-C cells and co-localise in MCF7 cells. Most importantly, the induction of caspase-2 activity is required for TRIM16 to initiate apoptosis. Our data suggest a novel mechanism by which TRIM16 can promote apoptosis by directly modulating caspase-2 activity.

Original languageEnglish
Pages (from-to)639-651
Number of pages13
JournalApoptosis
Volume18
Issue number5
DOIs
Publication statusPublished - 1 May 2013
Externally publishedYes

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Bibliographical note

Copyright The Author(s) 2013. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

Keywords

  • Apoptosis
  • Caspase-2
  • Cytochrome c
  • Mitochondrial depolarisation
  • TRIM16

Cite this

Kim, P. Y., Rahmanto, A. S., Tan, O., Norris, M. D., Haber, M., Marshall, G. M., & Cheung, B. B. (2013). TRIM16 overexpression induces apoptosis through activation of caspase-2 in cancer cells. Apoptosis, 18(5), 639-651. https://doi.org/10.1007/s10495-013-0813-y