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.
a Department of Medicine and Penn State Hershey Cancer Institute , Penn State College of Medicine , Hershey , PA , USA.
Jeffrey Q
JQ
Nguyen
a Department of Medicine and Penn State Hershey Cancer Institute , Penn State College of Medicine , Hershey , PA , USA.
Rosalyn B
RB
Irby
D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D047468:Immunoprecipitation; D013058:Mass Spectrometry; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D011379:Prognosis; D012261:Ribonucleoproteins / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D000099207:SS-A Antigen
D051017:Apoptosis Regulatory Proteins; D012261:Ribonucleoproteins; D000099207:SS-A Antigen; C101296:prostate apoptosis response-4 protein
Cisplatin; Par-4; TRIM21; colon cancer; pancreatic cancer; prognosis; proteasome