High TDP43 expression is required for TRIM16-induced inhibition of cancer cell growth and correlated with good prognosis of neuroblastoma and breast cancer patients

Patrick Y. Kim, Owen Tan, Bing Liu, Toby Trahair, Tao Liu, Michelle Haber, Murray D. Norris, Glenn M. Marshall, Belamy B. Cheung

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Tripartite Motif-containing protein 16 (TRIM16) is a member of a large family of tripartite motif (TRIM) proteins, that has been implicated in the pathogenesis of multiple cancers. However, the mechanism by which TRIM16 acts as a tumour suppressor is currently unknown. We used the versatile yeast two-hybrid assay on a cDNA library from human testes, which has relative high TRIM16 expression, to identify potential TRIM16-binding proteins. We identified transactive response DNA-binding protein 43 (TDP43) as a novel TRIM16 binding protein. Co-immunoprecipitation assay demonstrated that TDP43 bound TRIM16 in neuroblastoma and breast cancer cells. Enforced over-expression of TRIM16 increased the protein half-life of TDP43, through the inhibition of the proteosomal degradation pathway. High levels of TRIM16 and TDP43 are associated with good prognosis in both human neuroblastoma and breast cancer tissues. Importantly, we found TDP43 expression was required for TRIM16-induced inhibition of neuroblastoma and breast cancer cell growth and the repressive effect of TRIM16 on cell cycle regulatory proteins, E2F1 and pRb. Taken together, our data suggest that TRIM16 and TDP43 are both good prognosis indicators; also we showed that TRIM16 inhibits cancer cell viability by a novel mechanism involving interaction and stabilisation of TDP43 with consequent effects on E2F1 and pRb proteins.

LanguageEnglish
Pages315-323
Number of pages9
JournalCancer Letters
Volume374
Issue number2
DOIs
Publication statusPublished - 1 May 2016
Externally publishedYes

Fingerprint

DNA-Binding Proteins
Neuroblastoma
Breast Neoplasms
Growth
Neoplasms
Protein Binding
Tripartite Motif Proteins
Carrier Proteins
Cell Cycle Proteins
Two-Hybrid System Techniques
Gene Library
Immunoprecipitation
Half-Life
Testis
Cell Survival
Proteins

Keywords

  • Breast cancer
  • Neuroblastoma
  • TDP43
  • TRIM16
  • Yeast two-hybrid assay
  • RB/E2F PATHWAY
  • TDP-43

Cite this

Kim, Patrick Y. ; Tan, Owen ; Liu, Bing ; Trahair, Toby ; Liu, Tao ; Haber, Michelle ; Norris, Murray D. ; Marshall, Glenn M. ; Cheung, Belamy B. / High TDP43 expression is required for TRIM16-induced inhibition of cancer cell growth and correlated with good prognosis of neuroblastoma and breast cancer patients. In: Cancer Letters. 2016 ; Vol. 374, No. 2. pp. 315-323.
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abstract = "Tripartite Motif-containing protein 16 (TRIM16) is a member of a large family of tripartite motif (TRIM) proteins, that has been implicated in the pathogenesis of multiple cancers. However, the mechanism by which TRIM16 acts as a tumour suppressor is currently unknown. We used the versatile yeast two-hybrid assay on a cDNA library from human testes, which has relative high TRIM16 expression, to identify potential TRIM16-binding proteins. We identified transactive response DNA-binding protein 43 (TDP43) as a novel TRIM16 binding protein. Co-immunoprecipitation assay demonstrated that TDP43 bound TRIM16 in neuroblastoma and breast cancer cells. Enforced over-expression of TRIM16 increased the protein half-life of TDP43, through the inhibition of the proteosomal degradation pathway. High levels of TRIM16 and TDP43 are associated with good prognosis in both human neuroblastoma and breast cancer tissues. Importantly, we found TDP43 expression was required for TRIM16-induced inhibition of neuroblastoma and breast cancer cell growth and the repressive effect of TRIM16 on cell cycle regulatory proteins, E2F1 and pRb. Taken together, our data suggest that TRIM16 and TDP43 are both good prognosis indicators; also we showed that TRIM16 inhibits cancer cell viability by a novel mechanism involving interaction and stabilisation of TDP43 with consequent effects on E2F1 and pRb proteins.",
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High TDP43 expression is required for TRIM16-induced inhibition of cancer cell growth and correlated with good prognosis of neuroblastoma and breast cancer patients. / Kim, Patrick Y.; Tan, Owen; Liu, Bing; Trahair, Toby; Liu, Tao; Haber, Michelle; Norris, Murray D.; Marshall, Glenn M.; Cheung, Belamy B.

In: Cancer Letters, Vol. 374, No. 2, 01.05.2016, p. 315-323.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - High TDP43 expression is required for TRIM16-induced inhibition of cancer cell growth and correlated with good prognosis of neuroblastoma and breast cancer patients

AU - Kim, Patrick Y.

AU - Tan, Owen

AU - Liu, Bing

AU - Trahair, Toby

AU - Liu, Tao

AU - Haber, Michelle

AU - Norris, Murray D.

AU - Marshall, Glenn M.

AU - Cheung, Belamy B.

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KW - Neuroblastoma

KW - TDP43

KW - TRIM16

KW - Yeast two-hybrid assay

KW - RB/E2F PATHWAY

KW - TDP-43

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T2 - Cancer Letters

JF - Cancer Letters

SN - 0304-3835

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