Inhibition of GLUD1 mediated by LASP1 and SYVN1 contributes to hepatitis B virus X protein-induced hepatocarcinogenesis
© The Author(s) 2024. Published by Oxford University Press on behalf of Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences..
Glutamate dehydrogenase 1 (GLUD1) is implicated in oncogenesis. However, little is known about the relationship between GLUD1 and hepatocellular carcinoma (HCC). In the present study, we demonstrated that the expression levels of GLUD1 significantly decreased in tumors, which was relevant to the poor prognosis of HCC. Functionally, GLUD1 silencing enhanced the growth and migration of HCC cells. Mechanistically, the upregulation of interleukin-32 through AKT activation contributes to GLUD1 silencing-facilitated hepatocarcinogenesis. The interaction between GLUD1 and AKT, as well as α-ketoglutarate regulated by GLUD1, can suppress AKT activation. In addition, LIM and SH3 protein 1 (LASP1) interacts with GLUD1 and induces GLUD1 degradation via the ubiquitin-proteasome pathway, which relies on the E3 ubiquitin ligase synoviolin (SYVN1), whose interaction with GLUD1 is enhanced by LASP1. In hepatitis B virus (HBV)-related HCC, the HBV X protein (HBX) can suppress GLUD1 with the participation of LASP1 and SYVN1. Collectively, our data suggest that GLUD1 silencing is significantly associated with HCC development, and LASP1 and SYVN1 mediate the inhibition of GLUD1 in HCC, especially in HBV-related tumors.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - year:2024 |
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| Enthalten in: |
Journal of molecular cell biology - (2024) vom: 08. Apr. |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
You, Hong-Juan [VerfasserIn] |
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Date Revised 08.04.2024 published: Print-Electronic Citation Status Publisher |
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| doi: |
10.1093/jmcb/mjae014 |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM37077244X |
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| 520 | |a © The Author(s) 2024. Published by Oxford University Press on behalf of Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences. | ||
| 520 | |a Glutamate dehydrogenase 1 (GLUD1) is implicated in oncogenesis. However, little is known about the relationship between GLUD1 and hepatocellular carcinoma (HCC). In the present study, we demonstrated that the expression levels of GLUD1 significantly decreased in tumors, which was relevant to the poor prognosis of HCC. Functionally, GLUD1 silencing enhanced the growth and migration of HCC cells. Mechanistically, the upregulation of interleukin-32 through AKT activation contributes to GLUD1 silencing-facilitated hepatocarcinogenesis. The interaction between GLUD1 and AKT, as well as α-ketoglutarate regulated by GLUD1, can suppress AKT activation. In addition, LIM and SH3 protein 1 (LASP1) interacts with GLUD1 and induces GLUD1 degradation via the ubiquitin-proteasome pathway, which relies on the E3 ubiquitin ligase synoviolin (SYVN1), whose interaction with GLUD1 is enhanced by LASP1. In hepatitis B virus (HBV)-related HCC, the HBV X protein (HBX) can suppress GLUD1 with the participation of LASP1 and SYVN1. Collectively, our data suggest that GLUD1 silencing is significantly associated with HCC development, and LASP1 and SYVN1 mediate the inhibition of GLUD1 in HCC, especially in HBV-related tumors | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a GLUD1 | |
| 650 | 4 | |a HBX | |
| 650 | 4 | |a LASP1 | |
| 650 | 4 | |a SYVN1 | |
| 650 | 4 | |a hepatocellular carcinoma | |
| 700 | 1 | |a Li, Qi |e verfasserin |4 aut | |
| 700 | 1 | |a Ma, Li-Hong |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Xing |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Huan-Yang |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Yu-Xin |e verfasserin |4 aut | |
| 700 | 1 | |a Bao, En-Si |e verfasserin |4 aut | |
| 700 | 1 | |a Zhong, Yu-Jie |e verfasserin |4 aut | |
| 700 | 1 | |a Kong, De-Long |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Xiang-Ye |e verfasserin |4 aut | |
| 700 | 1 | |a Kong, Fan-Yun |e verfasserin |4 aut | |
| 700 | 1 | |a Zheng, Kui-Yang |e verfasserin |4 aut | |
| 700 | 1 | |a Tang, Ren-Xian |e verfasserin |4 aut | |
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