UBE2G2 inhibits vasculogenic mimicry and metastasis of uveal melanoma by promoting ubiquitination of LGALS3BP DOI Creative Commons
Andi Zhao,

Chenyu Zhou,

Jin-Jing Li

et al.

Acta Pharmaceutica Sinica B, Journal Year: 2024, Volume and Issue: 14(12), P. 5201 - 5218

Published: Sept. 13, 2024

Uveal melanoma (UM) poses a significant lethality, with approximately 50% of those developing metastases surviving less than one year. In the progression UM, vasculogenic mimicry (VM) induced by hypoxia plays pivotal role, which also partially explains resistance UM to anti-angiogenic therapies. Nevertheless, crucial molecular mechanisms underlying VM in remain unclear. We identified ubiquitin conjugating enzyme E2 G2 (UBE2G2) as critical suppressor through transcriptomic sequencing and metastasis correlation screening. hypoxia-induced are markedly exacerbated UBE2G2 knockdown significantly alleviated its overexpression. Mechanistically, directly binds galectin 3 binding protein (LGALS3BP) forms complex E3 ligase tripartite motif containing 38 (TRIM38), facilitating ubiquitination-mediated degradation LGALS3BP at K104 residue. Furthermore, inhibits oncogenic phenotypes inactivating intracellular PI3K/AKT signaling reprogramming tumor microenvironment. Therefore, targeting intercellular hypoxia-UBE2G2-LGALS3BP axis may contribute various therapeutic strategies for UM.

Language: Английский

Dysregulation of deubiquitinylases: a linchpin of gastrointestinal diseases DOI Creative Commons

Lorena Ferino,

Michael Naumann

Trends in Molecular Medicine, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

Citations

0
Caspase 3-specific cleavage of ubiquitin-specific peptidase 48 enhances drug-induced apoptosis in AML DOI Creative Commons
Zhanglin Zhang,

Xiang Lin,

Ya‐Ling Yang

et al.

Cancer Biology & Therapy, Journal Year: 2025, Volume and Issue: 26(1)

Published: Jan. 29, 2025

Dysfunction or dysregulation of deubiquitination is closely related to the initiation and development multiple cancers. Targeted regulation has been recognized as an important strategy in tumor therapy. However, mechanism by which drugs regulate deubiquitinase not clear. Here, we identified ubiquitin-specific peptidase 48 (USP48), a member protease family highly expressed various tumors, specific substrate for activated caspase-3. During drug induced apoptosis AML cells, caspase-3 cleaves USP48 through recognizing conservative motif DEQD located at 611–614 sites human USP48. Subsequent analysis showed that cleavage N-terminal fragment contains catalytic active domain easily degraded ubiquitination. Meanwhile knockdown experiment inhibiting expression could also promotes enhance efficacy chemotherapy drugs. Altogether, these results suggest targeting may represent novel therapeutic AML.

Language: Английский

Citations

0
USP48 inhibits colorectal cancer progression and promotes M1-like macrophage polarization by stabilizing TAK1 DOI
Xinwen Zhang, Jiawei Zhao,

Guangying Qi

et al.

Experimental Cell Research, Journal Year: 2025, Volume and Issue: 446(1), P. 114469 - 114469

Published: Feb. 18, 2025

Language: Английский

Citations

0
CDK1-mediated phosphorylation of USP37 regulates SND1 stability and promotes oncogenesis in colorectal cancer DOI Creative Commons
Liang Wu, Can Cheng, Ning Zhao

et al.

Acta Pharmaceutica Sinica B, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 1, 2025

Language: Английский

Citations

0
Therapeutic potential of targeting ubiquitin-specific proteases in colorectal cancer DOI
Chern Ein Oon,

Padmanabhan Anbazhagan,

Chong Teik Tan

et al.

Drug Discovery Today, Journal Year: 2025, Volume and Issue: unknown, P. 104356 - 104356

Published: April 1, 2025

Language: Английский

Citations

0
USP39 promote post-translational modifiers to stimulate the progress of cancer DOI Creative Commons
Yuli Zhou, Fang Wang,

Siren Feng

et al.

Discover Oncology, Journal Year: 2025, Volume and Issue: 16(1)

Published: May 13, 2025

Language: Английский

Citations

0
A phosphoglycerate mutase 1 allosteric inhibitor restrains TAM-mediated colon cancer progression DOI Creative Commons
Cheng Wang, Minghao Zhang, Shunyao Li

et al.

Acta Pharmaceutica Sinica B, Journal Year: 2024, Volume and Issue: 14(11), P. 4819 - 4831

Published: Sept. 14, 2024

Colorectal cancer (CRC) is a prevalent malignant tumor often leading to liver metastasis and mortality. Despite some success with PD-1/PD-L1 immunotherapy, the response rate for colon patients remains relatively low. This closely related immunosuppressive microenvironment mediated by tumor-associated macrophages (TAMs). Our previous work identified that phosphoglycerate mutase 1 (PGAM1) allosteric inhibitor, HKB99, exerts range of anti-tumor activities in lung cancer. Here, we found upregulation

Language: Английский

Citations

2
USP20 mediates malignant phenotypic changes in bladder cancer through direct interactions with YAP1 DOI Creative Commons

Wenwen CHEN,

Siqi Wu, Yifan Chen

et al.

Neoplasia, Journal Year: 2024, Volume and Issue: 60, P. 101102 - 101102

Published: Dec. 13, 2024

Language: Английский

Citations

0
UBE2G2 inhibits vasculogenic mimicry and metastasis of uveal melanoma by promoting ubiquitination of LGALS3BP DOI Creative Commons
Andi Zhao,

Chenyu Zhou,

Jin-Jing Li

et al.

Acta Pharmaceutica Sinica B, Journal Year: 2024, Volume and Issue: 14(12), P. 5201 - 5218

Published: Sept. 13, 2024

Uveal melanoma (UM) poses a significant lethality, with approximately 50% of those developing metastases surviving less than one year. In the progression UM, vasculogenic mimicry (VM) induced by hypoxia plays pivotal role, which also partially explains resistance UM to anti-angiogenic therapies. Nevertheless, crucial molecular mechanisms underlying VM in remain unclear. We identified ubiquitin conjugating enzyme E2 G2 (UBE2G2) as critical suppressor through transcriptomic sequencing and metastasis correlation screening. hypoxia-induced are markedly exacerbated UBE2G2 knockdown significantly alleviated its overexpression. Mechanistically, directly binds galectin 3 binding protein (LGALS3BP) forms complex E3 ligase tripartite motif containing 38 (TRIM38), facilitating ubiquitination-mediated degradation LGALS3BP at K104 residue. Furthermore, inhibits oncogenic phenotypes inactivating intracellular PI3K/AKT signaling reprogramming tumor microenvironment. Therefore, targeting intercellular hypoxia-UBE2G2-LGALS3BP axis may contribute various therapeutic strategies for UM.

Language: Английский

Citations

0