| 1997 |
UBE2E2 protein forms a thioester bond with ubiquitin in an E1-dependent manner, confirming it is a functional ubiquitin-conjugating E2 enzyme. Its UBC domain shares >90% identity with human UbcH6, mouse UbcM2, and Drosophila UbcD2, and the gene was mapped to chromosome 3p24.2. |
In vitro thioester bond formation assay (E1-dependent ubiquitin loading), cDNA cloning, amino acid sequence analysis, fluorescence in situ hybridization (FISH) |
Cytogenetics and cell genetics |
High |
9371400
|
| 2023 |
UBE2E2 interacts directly with Nrf2 via its N-terminal region (residues 1–52), promotes p62 accumulation and Nrf2-ARE antioxidant signaling, and stabilizes Snail protein by inhibiting its ubiquitin-mediated degradation, thereby driving EMT in ovarian cancer cells. Mutation of the active-site cysteine (Cys139) impaired both UBE2E2 function and its cellular distribution. |
Co-immunoprecipitation (co-IP), immunofluorescence, N-terminal deletion/truncation mapping, active-site cysteine mutagenesis (Cys139), siRNA knockdown and overexpression with migration/EMT readouts, xenograft mouse model |
Cell death & disease |
Medium |
36765041
|
| 2024 |
UBE2E2 mediates elongation of polyubiquitin chains in cooperation with the Nedd4 E3 ubiquitin ligase, as shown by ubiquitination assays in pancreatic β-cell-specific transgenic mice. Overexpression of UBE2E2 suppressed β-cell proliferation (associated with elevated p21 expression) and reduced β-cell mass, leading to glucose intolerance, without directly impairing glucose-stimulated insulin secretion from isolated islets. |
Ubiquitination assay, proteomic analysis of polyubiquitin chain types, pancreatic β-cell-specific transgenic mouse model, islet isolation/glucose-stimulated insulin secretion assay, gene expression analysis (p21), high-fat diet challenge |
Diabetes |
Medium |
38064504
|
| 2017 |
In rat liver cells, downregulation of UBE2E2 leads to accumulation of its ubiquitination target proteins phosphorylated c-MYC, KDM4A, and KMT5A (but not p21WAF1/CIP1), resulting in increased cell proliferation (PCNA+) and slowed DNA damage response (γH2AX+) in GST-P+ preneoplastic foci. |
Immunohistochemistry for ubiquitination target proteins (p-c-MYC, KDM4A, KMT5A, p21), PCNA and γH2AX staining, rat hepatocarcinogenesis model with thioacetamide treatment |
Toxicology and applied pharmacology |
Low |
28899750
|
| 2024 |
CRISPR excision of noncoding SNV-containing regions near UBE2E2 and CRISPRi screening across the locus suggest that T2D-associated noncoding variants concomitantly regulate UBE2E2, the neighboring UBE2E1, and other locus genes; compound heterozygous loss of both Ube2e2 and Ube2e1 in mice better replicated pathological adiposity and metabolic phenotypes than loss of either gene alone, implicating polygenic regulatory effects. |
CRISPR excision of noncoding regions, CRISPRi regulatory screen, compound heterozygous mouse knockouts, ex vivo adipogenesis assays, diet-induced obesity model |
JCI insight |
Medium |
39656538
|