ASB3 promotes hepatocellular carcinoma progression by mediating DR5 ubiquitination in TRAIL resistance
© 2024 Federation of American Societies for Experimental Biology..
Ankyrin-repeat proteins with a suppressor of cytokine signaling box (ASB) proteins belong to the E3 ubiquitin ligase family. 18 ASB members have been identified whose biological functions are mostly unexplored. Here, we discovered that ASB3 was essential for hepatocellular carcinoma (HCC) development and high ASB3 expression predicted poor clinical outcomes. ASB3 silencing induced HCC cell growth arrest and apoptosis in vitro and in vivo. Liver-specific deletion of Asb3 gene suppressed diethylnitrosamine (DEN)-induced liver cancer development. Mechanistically, ASB3 interacted with death receptor 5 (DR5), which promoted ubiquitination and degradation of DR5. We further showed that ASB3 knockdown stabilized DR5 and increased the sensitivity of liver cancer cells to the treatment of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) in a DR5-dependent manner in cellular and in animal models. In summary, we demonstrated that ASB3 promoted ubiquitination and degradation of DR5 in HCC, suggesting the potential of targeting ASB3 to HCC treatment and overcome TRAIL resistance.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2024 |
|---|---|
| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:38 |
|---|---|
| Enthalten in: |
FASEB journal : official publication of the Federation of American Societies for Experimental Biology - 38(2024), 4 vom: 29. Feb., Seite e23475 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Huang, Linlin [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
ASB3 |
|---|
| Anmerkungen: |
Date Completed 15.02.2024 Date Revised 15.02.2024 published: Print Citation Status MEDLINE |
|---|
| doi: |
10.1096/fj.202301755R |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM368239330 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM368239330 | ||
| 003 | DE-627 | ||
| 005 | 20240215232048.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 240209s2024 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1096/fj.202301755R |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1294.xml |
| 035 | |a (DE-627)NLM368239330 | ||
| 035 | |a (NLM)38334450 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Huang, Linlin |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a ASB3 promotes hepatocellular carcinoma progression by mediating DR5 ubiquitination in TRAIL resistance |
| 264 | 1 | |c 2024 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 15.02.2024 | ||
| 500 | |a Date Revised 15.02.2024 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2024 Federation of American Societies for Experimental Biology. | ||
| 520 | |a Ankyrin-repeat proteins with a suppressor of cytokine signaling box (ASB) proteins belong to the E3 ubiquitin ligase family. 18 ASB members have been identified whose biological functions are mostly unexplored. Here, we discovered that ASB3 was essential for hepatocellular carcinoma (HCC) development and high ASB3 expression predicted poor clinical outcomes. ASB3 silencing induced HCC cell growth arrest and apoptosis in vitro and in vivo. Liver-specific deletion of Asb3 gene suppressed diethylnitrosamine (DEN)-induced liver cancer development. Mechanistically, ASB3 interacted with death receptor 5 (DR5), which promoted ubiquitination and degradation of DR5. We further showed that ASB3 knockdown stabilized DR5 and increased the sensitivity of liver cancer cells to the treatment of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) in a DR5-dependent manner in cellular and in animal models. In summary, we demonstrated that ASB3 promoted ubiquitination and degradation of DR5 in HCC, suggesting the potential of targeting ASB3 to HCC treatment and overcome TRAIL resistance | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a ASB3 | |
| 650 | 4 | |a DR5 ubiquitination | |
| 650 | 4 | |a HCC | |
| 650 | 4 | |a TRAIL resistance | |
| 650 | 4 | |a apoptosis | |
| 650 | 7 | |a Ligands |2 NLM | |
| 650 | 7 | |a TNF-Related Apoptosis-Inducing Ligand |2 NLM | |
| 650 | 7 | |a Tumor Necrosis Factor-alpha |2 NLM | |
| 650 | 7 | |a ASB3 protein, human |2 NLM | |
| 700 | 1 | |a Che, Zhihui |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Fuchen |e verfasserin |4 aut | |
| 700 | 1 | |a Ge, Mengxiao |e verfasserin |4 aut | |
| 700 | 1 | |a Wu, Zhaohui |e verfasserin |4 aut | |
| 700 | 1 | |a Wu, Lijun |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Wenwen |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Zuoyun |e verfasserin |4 aut | |
| 700 | 1 | |a Zhu, Zhiling |e verfasserin |4 aut | |
| 700 | 1 | |a Xu, Wei |e verfasserin |4 aut | |
| 700 | 1 | |a Dong, Qiongzhu |e verfasserin |4 aut | |
| 700 | 1 | |a Yang, Dongqin |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t FASEB journal : official publication of the Federation of American Societies for Experimental Biology |d 1989 |g 38(2024), 4 vom: 29. Feb., Seite e23475 |w (DE-627)NLM01261730X |x 1530-6860 |7 nnns |
| 773 | 1 | 8 | |g volume:38 |g year:2024 |g number:4 |g day:29 |g month:02 |g pages:e23475 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1096/fj.202301755R |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 38 |j 2024 |e 4 |b 29 |c 02 |h e23475 | ||