Monoglyceride lipase mediates tumor-suppressive effects by promoting degradation of X-linked inhibitor of apoptosis protein
We have previously reported that Monoglyceride Lipase (MGL) expression is absent or reduced in various human malignancies and MGL-deficient mice develop tumors in multiple organs. Evidence also suggests MGL to be a tumor suppressor, however, the mechanisms underlying its tumor-suppressive actions remain to be investigated. Here, we report a novel function of MGL as a negative regulator of XIAP, an important inhibitor of apoptosis. We found that MGL directly interacted with XIAP and enhanced E3-ligase activity and proteasomal degradation of XIAP. MGL overexpression induced cell death that was coupled with caspase activation and reduced XIAP levels. N-terminus of MGL was found to mediate interactions with XIAP and induce cell death. MGL-deficient cells exhibited elevated XIAP levels and exhibited resistance to anticancer drugs. XIAP expression was significantly elevated in tissues of MGL-deficient animals as well as human lung cancers exhibiting reduced MGL expression. Thus, MGL appears to mediate its tumor-suppressive actions by inhibiting XIAP to induce cell death.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2020 |
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| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:27 |
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| Enthalten in: |
Cell death and differentiation - 27(2020), 10 vom: 06. Okt., Seite 2888-2903 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Liu, Renyan [VerfasserIn] |
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| Links: |
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| Themen: |
Birc4 protein, mouse |
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| Anmerkungen: |
Date Completed 08.11.2021 Date Revised 08.11.2021 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1038/s41418-020-0549-5 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM309602475 |
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| 245 | 1 | 0 | |a Monoglyceride lipase mediates tumor-suppressive effects by promoting degradation of X-linked inhibitor of apoptosis protein |
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| 520 | |a We have previously reported that Monoglyceride Lipase (MGL) expression is absent or reduced in various human malignancies and MGL-deficient mice develop tumors in multiple organs. Evidence also suggests MGL to be a tumor suppressor, however, the mechanisms underlying its tumor-suppressive actions remain to be investigated. Here, we report a novel function of MGL as a negative regulator of XIAP, an important inhibitor of apoptosis. We found that MGL directly interacted with XIAP and enhanced E3-ligase activity and proteasomal degradation of XIAP. MGL overexpression induced cell death that was coupled with caspase activation and reduced XIAP levels. N-terminus of MGL was found to mediate interactions with XIAP and induce cell death. MGL-deficient cells exhibited elevated XIAP levels and exhibited resistance to anticancer drugs. XIAP expression was significantly elevated in tissues of MGL-deficient animals as well as human lung cancers exhibiting reduced MGL expression. Thus, MGL appears to mediate its tumor-suppressive actions by inhibiting XIAP to induce cell death | ||
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| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
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| 700 | 1 | |a Curtiss, Christopher |e verfasserin |4 aut | |
| 700 | 1 | |a Sheikh, M Saeed |e verfasserin |4 aut | |
| 700 | 1 | |a Huang, Ying |e verfasserin |4 aut | |
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