Molecular mechanisms underlying the BIRC6-mediated regulation of apoptosis and autophagy
© 2024. The Author(s)..
Procaspase 9 is the initiator caspase for apoptosis, but how its levels and activities are maintained remains unclear. The gigantic Inhibitor-of-Apoptosis Protein BIRC6/BRUCE/Apollon inhibits both apoptosis and autophagy by promoting ubiquitylation of proapoptotic factors and the key autophagic protein LC3, respectively. Here we show that BIRC6 forms an anti-parallel U-shaped dimer with multiple previously unannotated domains, including a ubiquitin-like domain, and the proapoptotic factor Smac/DIABLO binds BIRC6 in the central cavity. Notably, Smac outcompetes the effector caspase 3 and the pro-apoptotic protease HtrA2, but not procaspase 9, for binding BIRC6 in cells. BIRC6 also binds LC3 through its LC3-interacting region, probably following dimer disruption of this BIRC6 region. Mutation at LC3 ubiquitylation site promotes autophagy and autophagic degradation of BIRC6. Moreover, induction of autophagy promotes autophagic degradation of BIRC6 and caspase 9, but not of other effector caspases. These results are important to understand how the balance between apoptosis and autophagy is regulated under pathophysiological conditions.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2024 |
|---|---|
| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:15 |
|---|---|
| Enthalten in: |
Nature communications - 15(2024), 1 vom: 30. Jan., Seite 891 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Liu, Shuo-Shuo [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
Caspases |
|---|
| Anmerkungen: |
Date Completed 01.02.2024 Date Revised 02.02.2024 published: Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1038/s41467-024-45222-1 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM367813459 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM367813459 | ||
| 003 | DE-627 | ||
| 005 | 20240202232211.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 240131s2024 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1038/s41467-024-45222-1 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1278.xml |
| 035 | |a (DE-627)NLM367813459 | ||
| 035 | |a (NLM)38291026 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Liu, Shuo-Shuo |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Molecular mechanisms underlying the BIRC6-mediated regulation of apoptosis and autophagy |
| 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 01.02.2024 | ||
| 500 | |a Date Revised 02.02.2024 | ||
| 500 | |a published: Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2024. The Author(s). | ||
| 520 | |a Procaspase 9 is the initiator caspase for apoptosis, but how its levels and activities are maintained remains unclear. The gigantic Inhibitor-of-Apoptosis Protein BIRC6/BRUCE/Apollon inhibits both apoptosis and autophagy by promoting ubiquitylation of proapoptotic factors and the key autophagic protein LC3, respectively. Here we show that BIRC6 forms an anti-parallel U-shaped dimer with multiple previously unannotated domains, including a ubiquitin-like domain, and the proapoptotic factor Smac/DIABLO binds BIRC6 in the central cavity. Notably, Smac outcompetes the effector caspase 3 and the pro-apoptotic protease HtrA2, but not procaspase 9, for binding BIRC6 in cells. BIRC6 also binds LC3 through its LC3-interacting region, probably following dimer disruption of this BIRC6 region. Mutation at LC3 ubiquitylation site promotes autophagy and autophagic degradation of BIRC6. Moreover, induction of autophagy promotes autophagic degradation of BIRC6 and caspase 9, but not of other effector caspases. These results are important to understand how the balance between apoptosis and autophagy is regulated under pathophysiological conditions | ||
| 650 | 4 | |a Journal Article | |
| 650 | 7 | |a Inhibitor of Apoptosis Proteins |2 NLM | |
| 650 | 7 | |a Caspases |2 NLM | |
| 650 | 7 | |a EC 3.4.22.- |2 NLM | |
| 650 | 7 | |a Mitochondrial Proteins |2 NLM | |
| 700 | 1 | |a Jiang, Tian-Xia |e verfasserin |4 aut | |
| 700 | 1 | |a Bu, Fan |e verfasserin |4 aut | |
| 700 | 1 | |a Zhao, Ji-Lan |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Guang-Fei |e verfasserin |4 aut | |
| 700 | 1 | |a Yang, Guo-Heng |e verfasserin |4 aut | |
| 700 | 1 | |a Kong, Jie-Yan |e verfasserin |4 aut | |
| 700 | 1 | |a Qie, Yun-Fan |e verfasserin |4 aut | |
| 700 | 1 | |a Wen, Pei |e verfasserin |4 aut | |
| 700 | 1 | |a Fan, Li-Bin |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Ning-Ning |e verfasserin |4 aut | |
| 700 | 1 | |a Gao, Ning |e verfasserin |4 aut | |
| 700 | 1 | |a Qiu, Xiao-Bo |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Nature communications |d 2010 |g 15(2024), 1 vom: 30. Jan., Seite 891 |w (DE-627)NLM199274525 |x 2041-1723 |7 nnns |
| 773 | 1 | 8 | |g volume:15 |g year:2024 |g number:1 |g day:30 |g month:01 |g pages:891 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1038/s41467-024-45222-1 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 15 |j 2024 |e 1 |b 30 |c 01 |h 891 | ||