title: TRIM16 overexpression induces apoptosis through activation of caspase-2 in cancer cells.
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.
authors: Children's Cancer Institute Australia for Medical Research, Randwick, NSW 2031, Australia.
authors: Patrick Y
authors: PY
authors: Kim
authors: Aldwin Suryo
authors: AS
authors: Rahmanto
authors: Owen
authors: O
authors: Tan
authors: Murray D
authors: MD
authors: Norris
authors: Michelle
authors: M
authors: Haber
authors: Glenn M
authors: GM
authors: Marshall
authors: Belamy B
authors: BB
authors: Cheung
mesh_terms: D017209:Apoptosis / Q000235:genetics*; D053143:Caspase 2 / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D003546:Cysteine Endopeptidases / Q000235:genetics* / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D004792:Enzyme Precursors / Q000235:genetics / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D057809:HEK293 Cells; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000235:genetics; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism; D009928:Organ Specificity; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D000070584:Tripartite Motif Proteins; D044767:Ubiquitin-Protein Ligases
chemical_list: D004268:DNA-Binding Proteins; D004792:Enzyme Precursors; D034741:RNA, Small Interfering; D014157:Transcription Factors; D000070584:Tripartite Motif Proteins; C117731:TRIM16 protein, human; D044767:Ubiquitin-Protein Ligases; C490360:CASP2 protein, human; D053143:Caspase 2; D003546:Cysteine Endopeptidases
references: FEBS Lett. 2002 Mar 27;515(1-3):66-70
references: 11943196
references: Oncogene. 2010 Nov 18;29(46):6172-83
references: 20729920
references: Apoptosis. 2012 Feb;17(2):200-16
references: 22002103
references: J Biol Chem. 2011 Jul 22;286(29):25729-38
references: 21628460
references: Mol Endocrinol. 1998 Nov;12(11):1733-48
references: 9817599
references: J Biol Chem. 2002 Aug 16;277(33):29803-9
references: 12065594
references: Proc Natl Acad Sci U S A. 2002 May 14;99(10):6871-6
references: 12011445
references: J Biol Chem. 2002 Apr 19;277(16):13430-7
references: 11832478
references: Cell Death Differ. 2006 Nov;13(11):1938-49
references: 16575408
references: Nat Rev Cancer. 2009 Dec;9(12):897-903
references: 19890334
references: J Biol Chem. 2006 Jun 30;281(26):18246-56
references: 16636064
references: Eur J Cell Biol. 2011 May;90(5):420-31
references: 21333377
references: Cell Death Differ. 2003 Jan;10(1):26-35
references: 12655293
references: Cell Death Differ. 2004 Nov;11(11):1234-41
references: 15297885
references: Proteins. 2010 Feb 15;78(3):790-5
references: 19967786
references: J Pathol. 2012 Feb;226(3):451-62
references: 22009481
references: Proc Natl Acad Sci U S A. 2007 Apr 10;104(15):6200-5
references: 17400754
references: Oncogene. 2009 May 7;28(18):1949-59
references: 19347032
references: Mol Cell. 2009 Sep 24;35(6):830-40
references: 19782032
references: Breast Cancer Res Treat. 2009 Sep;117(1):219-21
references: 18853248
references: J Biol Chem. 2002 Jun 7;277(23):20740-9
references: 11919186
references: Proc Natl Acad Sci U S A. 2009 Mar 31;106(13):5336-41
references: 19279217
references: J Biol Chem. 2011 Sep 30;286(39):34147-54
references: 21828056
references: PLoS One. 2012;7(5):e37470
references: 22629402
references: J Cell Biol. 2009 Apr 20;185(2):291-303
references: 19364921
references: Anal Biochem. 2009 Nov 1;394(1):68-74
references: 19595985
references: Nat Cell Biol. 2001 Nov;3(11):E255-63
references: 11715037
references: Cancer Lett. 2009 May 8;277(1):82-90
references: 19147277
references: J Cell Sci. 2011 Oct 15;124(Pt 20):3492-502
references: 21984809
references: Cell Cycle. 2010 Jan 1;9(1):12-3
references: 20016258
references: Cell Death Differ. 2006 Sep;13(9):1423-33
references: 16676004
references: J Biol Chem. 2003 Aug 22;278(34):31902-8
references: 12807881
references: Nat Rev Cancer. 2011 Oct 07;11(11):792-804
references: 21979307
references: J Cell Sci. 2005 Jan 15;118(Pt 2):265-7
references: 15654015
references: Cell Death Differ. 2003 Jan;10(1):101-7
references: 12655298
references: Cell Death Differ. 2004 Apr;11(4):439-47
references: 14713960