RACK1 Is an Interaction Partner of ATG5 and a Novel Regulator of Autophagy.
Autophagy is biological mechanism allowing recycling of long-lived proteins, abnormal protein aggregates, and damaged organelles under cellular stress conditions. Following sequestration in double- or multimembrane autophagic vesicles, the cargo is delivered to lysosomes for degradation. ATG5 is a key component of an E3-like ATG12-ATG5-ATG16 protein complex that catalyzes conjugation of the MAP1LC3 protein to lipids, thus controlling autophagic vesicle formation and expansion. Accumulating data indicate that ATG5 is a convergence point for autophagy regulation. Here, we describe the scaffold protein RACK1 (receptor activated C-kinase 1, GNB2L1) as a novel ATG5 interactor and an autophagy protein. Using several independent techniques, we showed that RACK1 interacted with ATG5. Importantly, classical autophagy inducers (starvation or mammalian target of rapamycin blockage) stimulated RACK1-ATG5 interaction. Knockdown of RACK1 or prevention of its binding to ATG5 using mutagenesis blocked autophagy activation. Therefore, the scaffold protein RACK1 is a new ATG5-interacting protein and an important and novel component of the autophagy pathways.
From the Molecular Biology, Genetics and Bioengineering Program, Sabanci University, Orhanli-Tuzla, 34956 Istanbul, Turkey.
Secil
S
Erbil
From the Molecular Biology, Genetics and Bioengineering Program, Sabanci University, Orhanli-Tuzla, 34956 Istanbul, Turkey.
Ozlem
O
Oral
From the Molecular Biology, Genetics and Bioengineering Program, Sabanci University, Orhanli-Tuzla, 34956 Istanbul, Turkey.
Geraldine
G
Mitou
From the Molecular Biology, Genetics and Bioengineering Program, Sabanci University, Orhanli-Tuzla, 34956 Istanbul, Turkey.
Cenk
C
Kig
From the Molecular Biology, Genetics and Bioengineering Program, Sabanci University, Orhanli-Tuzla, 34956 Istanbul, Turkey.
Emel
E
Durmaz-Timucin
the Department of Chemical and Biological Engineering and Center for Computational Biology and Bioinformatics, Koc University, 34450 Istanbul, Turkey.
Emine
E
Guven-Maiorov
From the Molecular Biology, Genetics and Bioengineering Program, Sabanci University, Orhanli-Tuzla, 34956 Istanbul, Turkey.
Ferah
F
Gulacti
From the Molecular Biology, Genetics and Bioengineering Program, Sabanci University, Orhanli-Tuzla, 34956 Istanbul, Turkey.
Gokcen
G
Gokce
the Department of Biology, University of Fribourg, Chemin du Musée 10, CH-1700 Fribourg, Switzerland, and.
Jörn
J
Dengjel
the Department of Biostatistics and Medical Informatics, School of Medicine, Acibadem University, Atasehir, 34752 İstanbul, Turkey.
Osman Ugur
OU
Sezerman
From the Molecular Biology, Genetics and Bioengineering Program, Sabanci University, Orhanli-Tuzla, 34956 Istanbul, Turkey, dgozuacik@sabanciuniv.edu.
Devrim
D
Gozuacik
D000818:Animals; D001343:Autophagy / Q000502:physiology*; D000071192:Autophagy-Related Protein 12 / Q000235:genetics / Q000378:metabolism; D000071187:Autophagy-Related Protein 5 / Q000378:metabolism*; D000071183:Autophagy-Related Proteins / Q000235:genetics / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D000075370:Receptors for Activated C Kinase; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*
C466624:ATG12 protein, human; C518959:ATG16L1 protein, human; C502778:ATG5 protein, human; D000071192:Autophagy-Related Protein 12; D000071187:Autophagy-Related Protein 5; D000071183:Autophagy-Related Proteins; D009363:Neoplasm Proteins; C419368:RACK1 protein, human; D000075370:Receptors for Activated C Kinase; D011956:Receptors, Cell Surface; D019204:GTP-Binding Proteins
ATG12-5-16; ATG5; RACK1; autophagy; lysosome; mammalian target of rapamycin (mTOR); p70S6K; protein-protein interaction; signaling