The SUMO ligase PIAS1 regulates UV-induced apoptosis by recruiting Daxx to SUMOylated foci.
J Cell Sci
; 125(Pt 23): 5819-29, 2012 Dec 01.
Article
en En
| MEDLINE
| ID: mdl-22976298
ABSTRACT
The small ubiquitin-like modifier (SUMO) ligase PIAS1 (Protein Inhibitor of Activated Stat-1) has been shown to play a role in cellular stress response by SUMOylating several proteins that are involved in DNA repair, apoptosis and transcription. In this paper, we show that PIAS1 regulates ultraviolet (UV)-induced apoptosis by recruiting Death-associated protein 6 (Daxx) to PIAS1-generated SUMO-foci. Cells that ectopically express PIAS1, but not other PIASes, show increased sensitivity to UV irradiation, suggesting that PIAS1 has a distinct function in UV-dependent apoptosis. Domain analysis of PIAS1 indicates that both PIAS1 SUMO-ligase activity and the specific localization of PIAS1 through its N-terminal and C-terminal domains are essential for UV-induced cell death. Daxx colocalizes with PIAS1-generated SUMOylated foci, and the reduction of Daxx using RNAi alleviates UV-induced apoptosis in PIAS1-expressing cells. PIAS1-mediated recruitment of Daxx and apoptosis following UV irradiation are dependent upon the Daxx C-terminal SUMO-interacting motif (SIM). Overall, our data suggest that the pro-apoptotic protein Daxx specifically interacts with one or more substrates SUMOylated by PIAS1 and this interaction leads to apoptosis following UV irradiation.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Rayos Ultravioleta
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Proteínas Nucleares
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Apoptosis
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Proteínas Modificadoras Pequeñas Relacionadas con Ubiquitina
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Proteínas Adaptadoras Transductoras de Señales
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Proteínas Inhibidoras de STAT Activados
Límite:
Humans
Idioma:
En
Año:
2012
Tipo del documento:
Article