Ube2j2, also known as Ubc6, is a ubiquitin-conjugating enzyme that functions in the ubiquitination of proteins, especially those at the endoplasmic reticulum (ER). It is involved in the endoplasmic reticulum-associated degradation (ERAD) pathway, which is crucial for maintaining protein homeostasis within the cell [3,4]. Ube2j2's role in ubiquitination is significant as it helps regulate multiple cellular processes, and its malfunction may lead to various disease states.

In acute myeloid leukemia (AML), genome-wide Nuclease technology screens using a mouse AML line insensitive to Venetoclax-induced mitochondrial apoptosis identified Ube2j2 as part of a synthetic lethal interaction. Depletion of Ube2j2, along with Ube2k, sensitized AML cells to Venetoclax in the presence of March5, suggesting a coordinated function with the E3 ligase March5 [2]. In hepatocellular carcinoma (HCC), Ube2j2 was highly expressed in cellular protrusions of metastatic HCC cells. Overexpression of Ube2j2 activated epithelial-mesenchymal transition in non-invasive HC cell lines and promoted invasion, while its silencing reduced cell invasion and endocytosis and downregulated p-EGFR expression [1].

In summary, Ube2j2 plays essential roles in protein ubiquitination and ER-associated degradation. Its study in model-based research, such as in AML and HCC models, has revealed its significance in drug sensitivity and cancer cell invasion respectively. Understanding Ube2j2's function provides insights into disease mechanisms, potentially guiding the development of novel therapeutic strategies for diseases like AML and HCC.