N-α-acetyltransferase 10 protein inhibits apoptosis through RelA/p65-regulated MCL1 expression.

N-α-Acetyltransferase 10 protein (Naa10p/ARD1), the catalytic subunit of N-acetyltransferase A, catalyzes both N-α-acetylation and ε-acetylation, as well as autoacetylation. Naa10p is involved in controlling cell proliferation, apoptosis, autophagy and neuronal development. Our group and others had reported prognostic value of Naa10p expression in various types of cancer. Despite the efforts to elucidate the biological function of Naa10p, it remains controversial regarding its roles in tumor development. Herein, we report that depletion of Naa10p inhibited the growth of xenograft tumors in nude mice. Microarray analysis identified MCL1 gene as one of targets downstream of Naa10p. Naa10p positively regulated MCL1 expression, as exogenous Naa10p promoted MCL1 expression, whereas Naa10p silencing decreased MCL1 expression. Ablation of Naa10p sensitized cancer cells to stimuli-induced apoptosis, and the anti-apoptotic function of Naa10p was, at least in part, mediated by MCL1. Mechanistically, we found a physical interaction between Naa10p and RelA/p65. Transcriptional activation of the MCL1 gene required the recruitment of Naa10p-RelA/p65 complex to the p65-binding site of MCL1 promoter region. We also demonstrated a positive correlation between MCL1 and Naa10p messenger RNA levels in both colon cancer and lung cancer tissues. These results indicate that Naa10p inhibits apoptosis through Naa10p-RelA/p65-dependent MCL1 transcriptional activation.