Snx4-assisted vacuolar targeting of transcription factors defines a new autophagy pathway for controlling ATG expression.
Autophagy
; 17(11): 3547-3565, 2021 11.
Article
em En
| MEDLINE
| ID: mdl-33678121
ABSTRACT
Autophagy, in part, is controlled by the repression and activation of autophagy-related (ATG) genes. Here, we describe a new selective autophagy pathway that targets functional transcriptional regulators to control their activity. This pathway is activated in response to nitrogen starvation and recycles transcriptional activators (Msn2 and Rim15) and a repressor (Ssn2/Med13) of ATG expression. Further analysis of Ssn2/Med13 vacuolar proteolysis revealed that this pathway utilizes the core autophagic machinery. However, it is independent of known nucleophagy mechanisms, receptor proteins, and the scaffold protein Atg11. Instead, Ssn2/Med13 exits the nucleus through the nuclear pore complex (NPC) and associates with the cytoplasmic nucleoporin Gle1, a member of the RNA remodeling complex. Dbp5 and Nup159, that act in concert with Gle1, are also required for Ssn2/Med13 clearance. Ssn2/Med13 is retrieved from the nuclear periphery and degraded by Atg17-initiated phagophores anchored to the vacuole. Efficient transfer to phagophores depends on the sorting nexin heterodimer Snx4/Atg24-Atg20, which binds to Atg17, and relocates to the perinucleus following nitrogen starvation. To conclude, this pathway defines a previously undescribed autophagy mechanism that targets select transcriptional regulators for rapid vacuolar proteolysis, utilizing the RNA remodeling complex, the sorting nexin heterodimer Snx4-Atg20, Atg17, and the core autophagic machinery. It is physiologically relevant as this Snx4-assisted vacuolar targeting pathway permits cells to fine-tune the autophagic response by controlling the turnover of both positive and negative regulators of ATG transcription.Abbreviations AIM:
Atg8 interacting motif; ATG autophagy-related; CKM CDK8 kinase module; IDR intrinsically disordered region; IP6 phosphoinositide inositol hexaphosphate; NPC nuclear pore complex; PAS phagophore assembly site; UPS ubiquitin-proteasomal system.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Autofagia
/
Fatores de Transcrição
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Proteínas de Saccharomyces cerevisiae
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Nexinas de Classificação
/
Proteínas Relacionadas à Autofagia
Tipo de estudo:
Prognostic_studies
Idioma:
En
Revista:
Autophagy
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Estados Unidos