title: Degradation of newly synthesized polypeptides by ribosome-associated RACK1/c-Jun N-terminal kinase/eukaryotic elongation factor 1A2 complex.
abstract: Folding of newly synthesized polypeptides (NSPs) into functional proteins is a highly regulated process. Rigorous quality control ensures that NSPs attain their native fold during or shortly after completion of translation. Nonetheless, signaling pathways that govern the degradation of NSPs in mammals remain elusive. We demonstrate that the stress-induced c-Jun N-terminal kinase (JNK) is recruited to ribosomes by the receptor for activated protein C kinase 1 (RACK1). RACK1 is an integral component of the 40S ribosome and an adaptor for protein kinases. Ribosome-associated JNK phosphorylates the eukaryotic translation elongation factor 1A isoform 2 (eEF1A2) on serines 205 and 358 to promote degradation of NSPs by the proteasome. These findings establish a role for a RACK1/JNK/eEF1A2 complex in the quality control of NSPs in response to stress.
authors.affiliation: Department of Biochemistry and Goodman Cancer Centre, McGill University, Montréal, Québec, Canada.
authors.forename: Valentina
authors.initials: V
authors.lastname: Gandin
authors.forename: Gustavo J
authors.initials: GJ
authors.lastname: Gutierrez
authors.forename: Laurence M
authors.initials: LM
authors.lastname: Brill
authors.forename: Tal
authors.initials: T
authors.lastname: Varsano
authors.forename: Yongmei
authors.initials: Y
authors.lastname: Feng
authors.forename: Pedro
authors.initials: P
authors.lastname: Aza-Blanc
authors.forename: Qingyan
authors.initials: Q
authors.lastname: Au
authors.forename: Shannon
authors.initials: S
authors.lastname: McLaughlan
authors.forename: Tiago A
authors.initials: TA
authors.lastname: Ferreira
authors.forename: Tommy
authors.initials: T
authors.lastname: Alain
authors.forename: Nahum
authors.initials: N
authors.lastname: Sonenberg
authors.forename: Ivan
authors.initials: I
authors.lastname: Topisirovic
authors.forename: Ze'ev A
authors.initials: ZA
authors.lastname: Ronai
mesh_terms: D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D019204:GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D048688:MAP Kinase Kinase 7 / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D020648:Peptide Elongation Factor 1 / Q000235:genetics / Q000378:metabolism*; D010455:Peptides / Q000378:metabolism*; D010766:Phosphorylation; D011132:Polyribosomes / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D055550:Protein Stability; D000075370:Receptors for Activated C Kinase; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D012270:Ribosomes / Q000378:metabolism; D012694:Serine / Q000378:metabolism; D015398:Signal Transduction
chemical_list: C503234:EEF1A2 protein, human; D009363:Neoplasm Proteins; D020648:Peptide Elongation Factor 1; D010455:Peptides; C419368:RACK1 protein, human; D000075370:Receptors for Activated C Kinase; D011956:Receptors, Cell Surface; D012694:Serine; D048031:JNK Mitogen-Activated Protein Kinases; D048688:MAP Kinase Kinase 7; C482569:MAP2K7 protein, human; D046988:Proteasome Endopeptidase Complex; D019204:GTP-Binding Proteins