Ube2e3, also known as UbcH9, is a ubiquitin-conjugating enzyme (E2). The ubiquitination process it participates in is crucial for various cellular functions, including the regulation of protein degradation, cell-cycle progression, and signal transduction pathways [5].

Loss-of-function experiments have revealed multiple roles of Ube2e3. Depletion of Ube2e3 in cells can induce cellular senescence, as seen in studies where cells lacking Ube2e3 show a distinct senescence-associated secretory phenotype, increased mitochondrial and lysosomal mass, and enhanced autophagic flux [2]. In bone marrow mesenchymal stem cells (BMSCs), knockdown of Ube2e3 accelerates cellular senescence and inhibits osteogenic differentiation, while overexpression has the opposite effects, suggesting its potential involvement in osteoporosis pathogenesis [1]. In breast cancer cells, targeting Ube2e3 with miR-379-5p affects cell viability, proliferation, and apoptosis [3]. In retinal pigment epithelial cells, depletion of Ube2e3 by siRNA leads to cell-cycle exit, indicating its essentiality for cell proliferation [4].

In conclusion, Ube2e3 is vital for regulating cellular senescence, proliferation, and differentiation processes. Studies using gene-knockout or knockdown models have provided insights into its role in diseases such as osteoporosis and cancer. Understanding Ube2e3's functions can potentially offer new therapeutic strategies for these age-related and malignant diseases.