JOURNAL ARTICLE

ATDC/TRIM29 phosphorylation by ATM/MAPKAP kinase 2 mediates radioresistance in pancreatic cancer cells

Lidong Wang, Huibin Yang, Phillip L Palmbos, Gina Ney, Taylor Ann Detzler, Dawn Coleman, Jacob Leflein, Mary Davis, Min Zhang, Wenhua Tang, J Kevin Hicks, Corey M Helchowski, Jayendra Prasad, Theodore S Lawrence, Liang Xu, Xiaochun Yu, Christine E Canman, Mats Ljungman, Diane M Simeone
Cancer Research 2014 March 15, 74 (6): 1778-88
24469230
Pancreatic ductal adenocarcinoma (PDAC) is characterized by therapeutic resistance for which the basis is poorly understood. Here, we report that the DNA and p53-binding protein ATDC/TRIM29, which is highly expressed in PDAC, plays a critical role in DNA damage signaling and radioresistance in pancreatic cancer cells. Ataxia-telangiectasia group D-associated gene (ATDC) mediated resistance to ionizing radiation in vitro and in vivo in mouse xenograft assays. ATDC was phosphorylated directly by MAPKAP kinase 2 (MK2) at Ser550 in an ATM-dependent manner. Phosphorylation at Ser-550 by MK2 was required for the radioprotective function of ATDC. Our results identify a DNA repair pathway leading from MK2 and ATM to ATDC, suggesting its candidacy as a therapeutic target to radiosensitize PDAC and improve the efficacy of DNA-damaging treatment.

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