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Autophagy. 2014 Mar;10(3):431-41. doi: 10.4161/auto.27344. Epub 2014 Jan 3.

Expression of the autophagy substrate SQSTM1/p62 is restored during prolonged starvation depending on transcriptional upregulation and autophagy-derived amino acids.

Author information

1
Department of Physiology and Cell Biology; Tokyo Medical and Dental University; Tokyo, Japan; Department of Biochemistry and Molecular Biology; Graduate School and Faculty of Medicine; University of Tokyo; Tokyo, Japan.
2
Department of Physiology and Cell Biology; Tokyo Medical and Dental University; Tokyo, Japan.

Abstract

SQSTM1/p62 (sequestosome 1) is a multifunctional signaling molecule, involved in a variety of cellular pathways. SQSTM1 is one of the best-known autophagic substrates, and is therefore widely used as an indicator of autophagic degradation. Here we report that the expression level of SQSTM1 can be restored during prolonged starvation. Upon starvation, SQSTM1 is initially degraded by autophagy. However, SQSTM1 is restored back to basal levels during prolonged starvation in mouse embryonic fibroblasts and HepG2 cells, but not in HeLa and HEK293 cells. Restoration of SQSTM1 depends on its transcriptional upregulation, which is triggered by amino acid starvation. Furthermore, amino acids derived from the autophagy-lysosome pathway are used for de novo synthesis of SQSTM1 under starvation conditions. The restoration of SQSTM1 is independent of reactivation of MTORC1 (mechanistic target of rapamycin complex 1). These results suggest that the expression level of SQSTM1 in starved cells is determined by at least 3 factors: autophagic degradation, transcriptional upregulation, and availability of lysosomal-derived amino acids. The results of this study also indicate that the expression level of SQSTM1 does not always inversely correlate with autophagic activity.

KEYWORDS:

SQSTM1/p62; amino acid; transcription

PMID:
24394643
PMCID:
PMC4077882
DOI:
10.4161/auto.27344
[Indexed for MEDLINE]
Free PMC Article

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