LAUSR

Simple Summary ATRX is one of the most frequently mutated tumor suppressor genes in human cancers. ATRX protein is a chromatin remodeler and transcriptional regulator that is essential for normal development. ATRX plays a crucial role in several essential cellular pathways, such as cooperating with DAXX to deposit histone variant H3.3 at repetitive regions, participating in chromatin remodeling, and responding to replication stress and DNA damage repair. ATRX mutations have been identified in several cancers and are considered important markers of clinical behavior, especially in glioma. The disruption of ATRX may contribute to cancer development and resistance to treatment. However, its role in tumorigenesis and the details of its mechanisms remain unclear. In this review, we will summarize the function of ATRX in normal biology and cancer and discuss the potential future direction of ATRX’s role in tumorigenesis. Understanding the functions of ATRX in cancers will help to develop more efficient and targeted anticancer therapies. Abstract The alpha-thalassemia mental retardation X-linked (ATRX) syndrome protein is a chromatin remodeling protein that primarily promotes the deposit of H3.3 histone variants in the telomere area. ATRX mutations not only cause ATRX syndrome but also influence development and promote cancer. The primary molecular characteristics of ATRX, including its molecular structures and normal and malignant biological roles, are reviewed in this article. We discuss the role of ATRX in its interactions with the histone variant H3.3, chromatin remodeling, DNA damage response, replication stress, and cancers, particularly gliomas, neuroblastomas, and pancreatic neuroendocrine tumors. ATRX is implicated in several important cellular processes and serves a crucial function in regulating gene expression and genomic integrity throughout embryogenesis. However, the nature of its involvement in the growth and development of cancer remains unknown. As mechanistic and molecular investigations on ATRX disclose its essential functions in cancer, customized therapies targeting ATRX will become accessible.