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.
| Language | English |
|---|---|
| Pages | 315-323 |
| Number of pages | 9 |
| Journal | Cancer Letters |
| Volume | 374 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - 1 May 2016 |
| Externally published | Yes |
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Keywords
- Breast cancer
- Neuroblastoma
- TDP43
- TRIM16
- Yeast two-hybrid assay
- RB/E2F PATHWAY
- TDP-43
Cite this
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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 journal › Article › Research › peer-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.
PY - 2016/5/1
Y1 - 2016/5/1
N2 - 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.
AB - 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.
KW - Breast cancer
KW - Neuroblastoma
KW - TDP43
KW - TRIM16
KW - Yeast two-hybrid assay
KW - RB/E2F PATHWAY
KW - TDP-43
UR - http://www.scopus.com/inward/record.url?scp=84959480883&partnerID=8YFLogxK
U2 - 10.1016/j.canlet.2016.02.021
DO - 10.1016/j.canlet.2016.02.021
M3 - Article
VL - 374
SP - 315
EP - 323
JO - Cancer Letters
T2 - Cancer Letters
JF - Cancer Letters
SN - 0304-3835
IS - 2
ER -