| Literature DB >> 24469230 |
Lidong Wang1, 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.
Abstract
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. ©2014 AACR.Entities:
Mesh：
Substances：
Year: 2014 PMID： 24469230 PMCID： PMC3961828 DOI： 10.1158/0008-5472.CAN-13-2289
Source DB: PubMed Journal: Cancer Res ISSN： 0008-5472 Impact factor: 12.701