Ask about this productRelated genes to: UBE4B antibody
- Gene:
- UBE4B NIH gene
- Name:
- ubiquitination factor E4B
- Previous symbol:
- -
- Synonyms:
- UBOX3, E4, UFD2, KIAA0684
- Chromosome:
- 1p36.22
- Locus Type:
- gene with protein product
- Date approved:
- 2000-01-28
- Date modifiied:
- 2016-10-05
Related products to: UBE4B antibody
Related articles to: UBE4B antibody
- Aberrant proteins are targeted for proteasomal degradation by polyubiquitylation catalyzed by sequential action of ubiquitin-activating enzymes (E1s), ubiquitin-conjugating enzymes (E2s), and ubiquitin ligases (E3s). A subset of proteasomal substrates require ubiquitin chain extension by ubiquitin-elongating enzymes (E4s) prior to proteolysis. We tested the requirement of Ufd2, the founding member of the E4 enzyme family, in resisting proteotoxic stress caused by the aminoglycoside hygromycin B in . The human homolog, UBE4B, is a potential therapeutic target for neurological disease and cancer. deletion sensitized yeast to hygromycin B, consistent with a role for the E4 in protein quality control. - Source: PubMed
Publication date: 2026/06/30
Paxton Kaikeyi MAvaala James ACreviston Chance SGumina JosephTrue Jason DRubenstein Eric M - Apoptosis, or programmed cell death, is a fundamental process essential for tissue homeostasis, development, and the elimination of damaged or potentially cancerous cells. Here, we identify the E3/E4 ubiquitin ligase UBE4B as a critical suppressor of apoptosis in p53-proficient tumor cells, functioning through a previously uncharacterized dual mechanism. Initially, an orthogonal ubiquitin transfer screening approach identified CCAR2 as a UBE4B substrate. We demonstrate that UBE4B interacts with and ubiquitinates CCAR2, promoting its proteasomal degradation. Furthermore, we found that UBE4B concurrently targets p53 itself for ubiquitin-dependent degradation. Functionally, UBE4B overexpression suppresses apoptosis, whereas rescue experiments indicate that restoring p53 expression reverses this suppression more effectively than restoring CCAR2, highlighting the dominance of the direct p53 degradation pathway. Mechanistically, UBE4B deficiency leads to CCAR2 accumulation, which inhibits SIRT1 activity, thereby enhancing p53 acetylation and stability; this effect is reversed upon CCAR2 co-depletion. Consistently, transcriptional profiling confirms that UBE4B downregulates key p53 target genes (e.g., BAX, PUMA) through this dual-pathway regulation. In summary, our study establishes that UBE4B acts as a key apoptosis suppressor by coordinately degrading both p53 and its positive regulator CCAR2, revealing a targetable vulnerability in p53-wild-type tumors. - Source: PubMed
Publication date: 2026/04/21
Jin BoQu JunyaoXu PengZhao BoJiao Xianting - Interleukin-33 (IL-33), a member of the IL-1 cytokine family, has emerged as a chromatin-associated cytokine with the potential to modulate gene expression through chromatin remodeling and epigenetic regulation. Despite its established role in immune responses, the specific genes regulated by nuclear IL-33 and its mechanisms remain elusive. Our research has found that overexpression of full-length IL-33 in human monocytes promotes the expression of the ubiquitin ligase UBE4B, leading to the ubiquitination and degradation of p53. Thence, our study indicates that full-length IL-33 can significantly inhibit the tumor suppressor p53, which may be the main reason for IL-33's impact on the macrophage polarization. Therefore, this study uncovers new functions of IL-33 in the nucleus and its role in macrophage behavior through p53 regulation. This insight could guide the development of targeted therapeutics for disorders involving macrophage dysregulation. - Source: PubMed
Publication date: 2026/04/03
Ren ShiyingLiu RenliYu YangyangLiu LipingLuo HaogeXu JinXie YingdongSun HaiyangZhang WenxinLi Dong - Proper crossover (CO) formation in meiosis serves dual roles in ensuring accurate chromosome segregation and generating genetic diversity. However, the molecular mechanisms underlying CO number and distribution remain incompletely understood. Previous studies have implicated the ubiquitin-proteasome system in CO regulation, but specific regulators and mechanisms are poorly defined. Here, we identify the E3 ubiquitin ligase Ufd2p as a key regulator promoting efficient CO formation through a focused genetic screen in . Deletion of significantly reduces CO frequency by enhancing the strength of CO interference. Integrated multiomics analysis indicates that Ufd2p targets Topoisomerase II (Top2p) for ubiquitination and subsequent proteasomal degradation during meiosis. Deletion of results in Top2p accumulation, which resolves DNA negative supercoils excessively and enhances CO interference in the nucleus, ultimately reducing CO numbers. We further show that the mammalian homolog of Ufd2p, UBE4B, plays a conserved role in promoting efficient CO formation by regulating TOP2A-dependent DNA negative supercoils dynamics. Notably, expression of mouse or human UBE4B in yeast restores CO formation and meiotic progression in deletion cells, demonstrating functional conservation across species. Together, our work identifies Ufd2p as a previously uncharacterized regulator of CO formation and provides important insights into the conserved molecular mechanism, which operates through Top2p-mediated supercoils homeostasis. - Source: PubMed
Publication date: 2026/02/06
Tan TaicongZhao YananChen YinghongMi YaliZeng JiaxinDu PengHan TingtingLiu YawenLi NingKong JunWang LiyingYu YangLi Mulin JunZhang LiangranLi WeiLiu Chao - Mitophagy, as a critical form of selective autophagy, plays a central role in maintaining cellular homeostasis. While the canonical PTEN-Induced Kinase 1 (PINK1)-Parkin pathway is well established, mitophagy can still be effectively induced in Parkin-deficient cells such as HeLa, indicating the existence of Parkin-independent alternative pathways. The mitochondrial matrix proteins 4-Nitrophenylphosphatase domain and non-neuronal SNAP25-like protein homolog 1 (NIPSNAP1) acts as a key effector in such pathways, yet its regulatory mechanisms remain incompletely understood. Here, we identify Ubiquitination Factor E4B (UBE4B) as an E3 ubiquitin ligase for NIPSNAP1 and demonstrate that it catalyzes NIPSNAP1 ubiquitination in both Human Embryonic Kidney 293 cells (HEK293T) and HeLa cells. Under mitochondrial depolarization, UBE4B not only promotes NIPSNAP1 ubiquitination and subsequent lysosome-dependent degradation, but also significantly enhances its interaction with the autophagy adaptors Nuclear Dot Protein 52 kDa (NDP52) and Sequestosome 1 (p62/SQSTM1). Notably, while Parkin does not ubiquitinate NIPSNAP1, UBE4B-mediated ubiquitination facilitates mitophagy in Parkin-null HeLa cells by strengthening the binding between NIPSNAP1 and NDP52. Collectively, this study unveils a novel mitophagy pathway regulated by the UBE4B-NIPSNAP1 axis, offering new insights into mitochondrial quality control. - Source: PubMed
Publication date: 2026/01/22
Jin BoQu JunyaoXu KeZhang YufeiXu PengWang XinZhao BoJiao Xianting