ARD1

Prostate cancer (PCa) is the second most common cancer in men. Androgen receptor (AR) signaling pathway plays a crucial role in prostate development and homeostasis. Dysregulation of this pathway activates AR leading to PCa pathogenesis and progression. AR binds testosterone and other male hormones, which then undergoes post-translational modification for AR nuclear translocation and transcriptional activation. AR activation by post-translational modification is thus imperative for PCa cell growth and survival. Identification and understanding of the pathological and mechanistic roles of AR modifications may increase our understanding of AR activation in PCa and provide new therapeutic options. Recently, AR acetylation has been described as an important step for AR activation. Upregulation of several acetyltransferases has been reported to be associated with PCa progression. Herein, we provide a general understanding of AR acetylation, with a special emphasis on ARD1, and potential therapies that may be exploited against the ARD1-AR axis for PCa treatment.

Hepatocellular carcinoma (HCC), a representative example of a malignancy with a poor prognosis, is characterized by high mortality because it is typically in an advanced stage at diagnosis and leaves very little hepatic functional reserve. Despite advances in medical and surgical techniques, there is no omnipotent tool that can diagnose HCC early and then cure it medically or surgically. Several recent studies have shown that a variety of pathways are involved in the development, growth, and even metastasis of HCC. Among a variety of cytokines or molecules, some investigators have suggested that arrest-defective 1 (ARD1), an acetyltransferase, plays a key role in the development of malignancies. Although ARD1 is thought to be centrally involved in the cell cycle, cell migration, apoptosis, differentiation, and proliferation, the role of ARD1 and its potential mechanistic involvement in HCC remain unclear. Here, we review the present literature on ARD1. First, we provide an overview of the essential structure, functions, and molecular mechanisms or pathways of ARD1 in HCC. Next, we discuss potential clinical implications and perspectives. We hope that, by providing new insights into ARD1, this review will help to guide the next steps in the development of markers for the early detection and prognosis of HCC.

Post-translational modifications (PTMs) are chemical alterations that occur in proteins that play critical roles in various cellular functions. Lysine acetylation is an important PTM in eukaryotes, and it is catalyzed by lysine acetyltransferases (KATs). KATs transfer acetyl-coenzyme A to the internal lysine residue of substrate proteins. Arrest defective 1 (ARD1) is a member of the KAT family. Since the identification of its KAT activity 15 years ago, many studies have revealed that diverse cellular proteins are acetylated by ARD1. ARD1-mediated lysine acetylation is a key switch that regulates the enzymatic activities and biological functions of proteins and influences cell biology from development to pathology. In this review, we summarize protein lysine acetylation mediated by ARD1 and describe the biological meanings of this modification.