1. Rack1 Is An Interaction Partner Of Atg5 And A Novel Regulator Of Autophagy
- Author
-
Jörn Dengjel, Ozlem Oral, Osman Ugur Sezerman, Emine Guven-Maiorov, Secil Erbil, Géraldine Mitou, Emel Durmaz-Timucin, Cenk Kig, Ferah Gulacti, Gokcen Gokce, Devrim Gozuacik, Acibadem University Dspace, Güven, Emine Maiorov, Erbil, Seçil, Oral, Özlem, Mitou, Geraldine, Kig, Cenk, Durmaz-Timuçin, Emel, Gülactı, Ferah, Gökçe, Gökçen, Dengjel, Jorn, Sezerman, Osman Uğur, Gözüaçık, Devrim, The Center for Computational Biology and Bioinformatics (CCBB), College of Engineering, and Department of Chemical and Biological Engineering
- Subjects
0301 basic medicine ,Scaffold protein ,Programmed cell death ,ATG5 ,Autophagy-Related Proteins ,Receptors, Cell Surface ,Biology ,BAG3 ,Receptors for Activated C Kinase ,Biochemistry ,Autophagy-Related Protein 5 ,03 medical and health sciences ,Mice ,Molecular biology ,GTP-Binding Proteins ,Lysosome ,medicine ,Autophagy ,Animals ,Humans ,Molecular Biology ,ATG16L1 ,Cell Biology ,Autophagy-related protein 13 ,Cell biology ,Neoplasm Proteins ,030104 developmental biology ,medicine.anatomical_structure ,HEK293 Cells ,Autophagy-Related Protein 12 ,Protein Binding - Abstract
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., Scientific and Technological Research Council of Turkey (TÜBİTAK); Sabanci University; Swiss National Science Foundation; Scientific and Technological Research Council of Turkey (TÜBİTAK); IKU Prof. Onder Oztunali Science Award; TGC Sedat Simavi Health Sciences Award; Elginkan Foundation Technology Award
- Published
- 2016