ING5: multifaceted roles beyond tumor suppression in cellular physiology and disease

ING5, initially identified as a tumor-suppressor, serves as a chromatin regulator with a diverse and extensive range of biological functions. This review undertakes an in-depth exploration of the structural characteristics and domain organization of ING family proteins, with a specific emphasis on ING5. The functional characteristics of ING5 are highly intricate and multi-dimensional. In the context of chromatin regulation and gene expression control, ING5 engages in interactions with diverse protein complexes through its conserved domains. It actively participates in the fine-tuning of chromatin structure and gene expression within tumor cells. Moreover, ING5 plays a pivotal and indispensable role in the regulation of DNA replication, cell cycle, and apoptosis, thereby exerting a profound influence on the fundamental biological processes of cells. Additionally, the binding properties and genomic associations of ING5 contribute significantly to its wide-ranging functions. ING5 exerts multiple and intricate action mechanisms in the processes of tumorigenesis, tumor development, and cancer treatment. It has substantial impacts on the biological behaviors of tumor cells, including proliferation, migration, and invasion. Furthermore, ING5 has emerged as a highly promising target for cancer therapy, presenting novel opportunities for the development of tumor-specific treatment strategies. Beyond its well-established role in tumor suppression, ING5 exhibits a diverse array of physiological functions. In the context of stem cell differentiation, ING5 regulates gene expression patterns, which are of utmost importance for determining cell fate. During embryonic development, it ensures the normal expression of genes associated with cell proliferation and differentiation, thereby being essential for the proper morphogenesis of the embryo. ING5 is also involved in metabolic regulation, particularly lipid metabolism, by modulating relevant genes to influence lipid levels. Additionally, it participates in the maintenance of vascular function by regulating the activities of vascular endothelial cells and angiogenesis, which are crucial for vascular homeostasis. This review comprehensively summarizes the extensive functions of ING5 as an epigenetic regulator in maintaining physiological homeostasis. By delving into its roles beyond tumor suppression, we aspire to attain a more comprehensive and in-depth understanding of its significance and potential implications in various biological processes and medical applications.