TRIM21 is a novel regulator of Par-4 in colon and pancreatic cancer cells.
The prostate apoptosis response protein 4 (Par-4) is a tumor-suppressor that has been shown to induce cancer-cell selective apoptosis in a variety of cancers. The regulation of Par-4 expression and activity is a relatively understudied area, and identifying novel regulators of Par-4 may serve as novel therapeutic targets. To identify ... novel regulators of Par-4, a co-immunoprecipitation was performed in colon cancer cells, and co-precipitated proteins were identified by mass-spectometry. TRIM21 was identified as a novel interacting partner of Par-4, and further shown to interact with Par-4 endogenously and through its PRY-SPRY domain. Additional studies show that TRIM21 downregulates Par-4 levels in response to cisplatin, and that TRIM21 can increase the resistance of colon cancer cells to cisplatin. Furthermore, forced Par-4 expression can sensitize pancreatic cancer cells to cisplatin. Finally, we demonstrate that TRIM21 expression predicts survival in pancreatic cancer patients. Our work highlights a novel mechanism of Par-4 regulation, and identifies a novel prognostic marker and potential therapeutic target for pancreatic cancer.
Mesh Terms:
Apoptosis Regulatory Proteins, Cell Line, Tumor, Colonic Neoplasms, Humans, Immunoprecipitation, Mass Spectrometry, Pancreatic Neoplasms, Prognosis, Ribonucleoproteins, Transfection
Apoptosis Regulatory Proteins, Cell Line, Tumor, Colonic Neoplasms, Humans, Immunoprecipitation, Mass Spectrometry, Pancreatic Neoplasms, Prognosis, Ribonucleoproteins, Transfection
Cancer Biol. Ther.
Date: Jan. 02, 2017
PubMed ID: 27830973
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