title: Glucose deprivation triggers protein kinase C-dependent β-catenin proteasomal degradation.
abstract: Autophagy is a conserved process that contributes to cell homeostasis. It is well known that induction mainly occurs in response to nutrient starvation, such as starvation of amino acids and insulin, and its mechanisms have been extensively characterized. However, the mechanisms behind cellular glucose deprivation-induced autophagy are as of now poorly understood. In the present study, we determined a mechanism by which glucose deprivation induced the PKC-dependent proteasomal degradation of β-catenin, leading to autophagy. Glucose deprivation was shown to cause a sub-G1 transition and enhancement of the LC3-II protein levels, whereas β-catenin protein underwent degradation in a proteasome-dependent manner. Moreover, the inhibition of GSK3β was unable to abolish the glucose deprivation-mediated β-catenin degradation or up-regulation of LC3-II protein levels, which suggested GSK3β-independent protein degradation. Intriguingly, the inhibition of PKCα using a pharmacological inhibitor and transfection of siRNA for PKCα was observed to effectively block glucose deprivation-induced β-catenin degradation as well as the increase in LC3-II levels and the accumulation of a sub-G1 population. Together, our results demonstrated a molecular mechanism by which glucose deprivation can induce the GSK3β-independent protein degradation of β-catenin, leading to autophagy.
authors.affiliation: From the Department of Biochemistry and Molecular Biology, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-752, Korea and.
authors.forename: Seung-Won
authors.initials: SW
authors.lastname: Choi
authors.affiliation: From the Department of Biochemistry and Molecular Biology, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-752, Korea and the Brain Korea 21 Plus Project for Medical Science, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-752, Korea.
authors.forename: Jun-Kyu
authors.initials: JK
authors.lastname: Song
authors.affiliation: From the Department of Biochemistry and Molecular Biology, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-752, Korea and the Brain Korea 21 Plus Project for Medical Science, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-752, Korea.
authors.forename: Ye-Seal
authors.initials: YS
authors.lastname: Yim
authors.affiliation: From the Department of Biochemistry and Molecular Biology, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-752, Korea and the Brain Korea 21 Plus Project for Medical Science, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-752, Korea.
authors.forename: Ho-Geun
authors.initials: HG
authors.lastname: Yun
authors.affiliation: From the Department of Biochemistry and Molecular Biology, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-752, Korea and the Brain Korea 21 Plus Project for Medical Science, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-752, Korea khchun@yuhs.ac.
authors.forename: Kyung-Hee
authors.initials: KH
authors.lastname: Chun
mesh_terms: D001343:Autophagy / Q000187:drug effects / Q000235:genetics; D002227:Carbazoles / Q000494:pharmacology; D002453:Cell Cycle / Q000187:drug effects / Q000235:genetics; D002460:Cell Line; D005947:Glucose / Q000378:metabolism* / Q000494:pharmacology; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D057809:HEK293 Cells; D006801:Humans; D015151:Immunoblotting; D018021:Lithium Chloride / Q000494:pharmacology; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D051571:Protein Kinase C-alpha / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D059748:Proteolysis; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*
chemical_list: D002227:Carbazoles; D051176:beta Catenin; C081021:Go 6976; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D051571:Protein Kinase C-alpha; D038362:Glycogen Synthase Kinase 3; D046988:Proteasome Endopeptidase Complex; D018021:Lithium Chloride; D005947:Glucose
keywords: Autophagy; Glucose; Glycogen Synthase Kinase 3 (GSK3); Protein Kinase C (PKC); beta-Catenin