ATDC/TRIM29 phosphorylation by ATM/MAPKAP kinase 2 mediates radioresistance in pancreatic cancer cells.
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.
Duke Scholars
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Related Subject Headings
- Xenograft Model Antitumor Assays
- Transcription Factors
- Radiation Tolerance
- Protein-Serine-Threonine Kinases
- Protein Serine-Threonine Kinases
- Protein Processing, Post-Translational
- Phosphorylation
- Phosphoproteins
- Pancreatic Neoplasms
- Oncology & Carcinogenesis
Citation
Published In
DOI
EISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Xenograft Model Antitumor Assays
- Transcription Factors
- Radiation Tolerance
- Protein-Serine-Threonine Kinases
- Protein Serine-Threonine Kinases
- Protein Processing, Post-Translational
- Phosphorylation
- Phosphoproteins
- Pancreatic Neoplasms
- Oncology & Carcinogenesis