Anti-ATAD2 monoclonal antibody, clone DM1293

ATPase family, AAA domain containing 2 (ATAD2) has been found overexpressed in various cancer types and correlated with malignant status and poor prognosis. However, little is known about the clinical significance of ATAD2 in gastric cancer patients. The aim of this study was to explore the clinical and prognostic significance of ATAD2 in gastric cancer. The mRNA and protein levels expression of ATAD2 were detected in clinical tissue samples by qRT-PCR and immunohistochemistry, respectively. We examined the ATAD2 protein expression by immunohistochemistry. Furthermore, we analyzed the association between ATAD2 expression and clinicopathological features including prognosis in 166 gastric cancer samples. In our results, ATAD2 mRNA and protein were highly expressed in gastric cancer samples. ATAD2 overexpression was correlated with advanced clinical stage, tumor depth, lymph node metastasis, and distant metastasis. According to the survival analysis, ATAD2 protein overexpression was a poor independent prognostic factor for gastric cancer patients. In summary, ATAD2 could serve as a prognostic biomarker for gastric cancer patients.

ATAD2 (ATPase family AAA domain-containing protein 2) is a chromatin regulator harboring an AAA+ ATPase domain and a bromodomain, previously proposed to function as an oncogenic transcription co-factor. Here we suggest that ATAD2 is also required for DNA replication. ATAD2 is co-expressed with genes involved in DNA replication in various cancer types and predominantly expressed in S phase cells where it localized on nascent chromatin (replication sites). Our extensive biochemical and cellular analyses revealed that ATAD2 is recruited to replication sites through a direct interaction with di-acetylated histone H4 at K5 and K12, indicative of newly synthesized histones during replication-coupled chromatin reassembly. Similar to ATAD2-depletion, ectopic expression of ATAD2 mutants that are deficient in binding to these di-acetylation marks resulted in reduced DNA replication and impaired loading of PCNA onto chromatin, suggesting relevance of ATAD2 in DNA replication. Taken together, our data show a novel function of ATAD2 in cancer and for the first time identify a reader of newly synthesized histone diacetylation-marks during replication.