UBE3D

Last update 08 May 2025

Basic Info

Synonyms

C6orf157, DKFZp434A1520, E3 ubiquitin-protein ligase E3D

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Introduction

E3 ubiquitin-protein ligase which accepts ubiquitin from specific E2 ubiquitin-conjugating enzymes, and transfers it to substrates, generally promoting their degradation by the proteasome.

100 Clinical Results associated with UBE3D

100 Translational Medicine associated with UBE3D

0 Patents (Medical) associated with UBE3D

Literatures (Medical) associated with UBE3D

01 Aug 2024·Molecular Cell

Cytoplasmic binding partners of the Integrator endonuclease INTS11 and its paralog CPSF73 are required for their nuclear function

Article

Author: Tong, Liang ; Chiang, Wesley ; Huang, Kai-Lieh ; Beam, Alissa C ; Pröschel, Christoph ; Wagner, Eric J ; Lin, Min-Han ; Jensen, Madeline K ; Williams, Kelsey ; Chu, Hsu-Feng ; Haseley, MaryClaire ; Russell, William K ; Elrod, Nathan D

INTS11 and CPSF73 are metal-dependent endonucleases for Integrator and pre-mRNA 3'-end processing, respectively. Here, we show that the INTS11 binding partner BRAT1/CG7044, a factor important for neuronal fitness, stabilizes INTS11 in the cytoplasm and is required for Integrator function in the nucleus. Loss of BRAT1 in neural organoids leads to transcriptomic disruption and precocious expression of neurogenesis-driving transcription factors. The structures of the human INTS9-INTS11-BRAT1 and Drosophila dIntS11-CG7044 complexes reveal that the conserved C terminus of BRAT1/CG7044 is captured in the active site of INTS11, with a cysteine residue directly coordinating the metal ions. Inspired by these observations, we find that UBE3D is a binding partner for CPSF73, and UBE3D likely also uses a conserved cysteine residue to directly coordinate the active site metal ions. Our studies have revealed binding partners for INTS11 and CPSF73 that behave like cytoplasmic chaperones with a conserved impact on the nuclear functions of these enzymes.

01 Feb 2024·Biochemical Genetics

Circ_0059457 Promotes Proliferation, Metastasis, Sphere Formation and Glycolysis in Breast Cancer Cells by Sponging miR-140-3p to Regulate UBE2C

Article

Author: Bai, Xiangdong ; Wang, Fan ; Han, Lei ; Xi, Zhibin ; Huang, Li ; Zhang, Guochen ; Han, Guohui

Circular RNA (circRNA) has been confirmed to regulate breast cancer (BC) progression. However, the role of circ_0059457 in BC progression is still unclear.The expression of circ_0059457, taspase 1 (TASP1), microRNA (miR)-140-3p and ubiquitin-binding enzyme E2C (UBE2C) was detected by quantitative real-time PCR. Cell proliferation, migration, invasion and sphere formation ability were assessed by cell counting kit-8 assay, EdU assay, wound healing assay, transwell assay and sphere formation assay. Cell glycolysis was assessed by detecting glucose uptake, lactate levels and ATP/ADP ratio. Dual-luciferase reporter assay, RIP assay, RNA pull-down assay were used to validate RNA interaction. Xenograft tumor model to assess the effect of circ_0059457 on BC tumor growth in vivo. Circ_0059457 had elevated expression in BC tissues and cells. Circ_0059457 knockdown inhibited BC cell proliferation, metastasis, sphere formation ability, and glycolysis. In terms of mechanism, circ_0059457 sponged miR-140-3p, and miR-140-3p targeted UBE2C. MiR-140-3p inhibition reversed the effect of circ_0059457 knockdown on BC cell malignant behaviors. Besides, miR-140-3p overexpression inhibited BC cell proliferation, metastasis, sphere formation ability and glycolysis, and these effects were abrogated by UBE2C enhancement. Furthermore, circ_0059457 regulated UBE2C expression through sponging miR-140-3p. Additionally, circ_0059457 knockdown obviously inhibited BC tumor growth in vivo. Circ_0059457 promoted BC progression via miR-140-3p/UBE2C axis, which provided potential target for the treatment of BC.

15 Dec 2023·Journal of Clinical Investigation

Active DHEA uptake in the prostate gland correlates with aggressive prostate cancer

Article

Author: Yan, Weiwei ; Tang, Huiru ; Ren, Ruobing ; Wu, Denglong ; Wang, Zengming ; Zhuang, Qian ; Yang, Tao ; Liu, Ying ; Li, Jing ; Tan, Qilong ; Zhang, Xuebin ; Wang, Zixian ; Wei, Gong-Hong ; Li, Zhenfei ; Wang, Chenyang ; Butler, William ; Li, Xin ; Huang, Shengsong ; Liu, Ziqun ; He, Dongyin

Strategies for patient stratification and early intervention are required to improve clinical benefits for patients with prostate cancer. Here, we found that active DHEA utilization in the prostate gland correlated with tumor aggressiveness at early disease stages, and 3βHSD1 inhibitors were promising for early intervention. [3H]-labeled DHEA consumption was traced in fresh prostatic biopsies ex vivo. Active DHEA utilization was more frequently found in patients with metastatic disease or therapy-resistant disease. Genetic and transcriptomic features associated with the potency of prostatic DHEA utilization were analyzed to generate clinically accessible approaches for patient stratification. UBE3D, by regulating 3βHSD1 homeostasis, was discovered to be a regulator of patient metabolic heterogeneity. Equilin suppressed DHEA utilization and inhibited tumor growth as a potent 3βHSD1 antagonist, providing a promising strategy for the early treatment of aggressive prostate cancer. Overall, our findings indicate that patients with active prostatic DHEA utilization might benefit from 3βHSD1 inhibitors as early intervention.

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UBE3D

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