The tumor suppressor, TAX1BP2, is a novel substrate of ATM kinase

Abstract

DNA damage repair response is a crucial process for cancer prevention. One of the key regulators of this process is ataxia telangiectasia mutated (ATM) kinase, which modulates the p53 level by direct and indirect phosphorylation. Recent data showed that ATM also localizes at the centrosome, but the function remains elusive. TAX1BP2 was initially identified as a novel centrosomal protein that interacts directly with the human T-cell leukemia virus type 1 (HTLV-1)-encoded oncoprotein, Tax, and inhibits centrosome overduplication. Subsequently, TAX1BP2 was found to be a tumor suppressor in hepatocellular carcinoma, and accumulation of TAX1BP2 was observed upon chemotherapeutic drug treatment. Here, we provide evidence that TAX1BP2 is a direct phosphorylation substrate of ATM. The protein level of TAX1BP2 is significantly upregulated in response to DNA damaging agents. Serine-922 of TAX1BP2 is the phosphorylation site of ATM, and such phosphorylation modulates the protein stability, ubiquitination and tumor suppressor activity of TAX1BP2. Taken together, we demonstrate for the first time that TAX1BP2 is a novel effector of ATM in DNA damage response and delineated a new mechanism by which ATM stabilizes the tumor suppressor TAX1BP2.