Phosphorylation of T107 by CamKIIδ Regulates the Detoxification Efficiency and Proteomic Integrity of Glyoxalase 1
Autor: | Aurelio A. Teleman, Jessy Chen, Peter P. Nawroth, Thomas Fleming, Johanna Zemva, Marta Campos Campos, Johannes Backs, Alireza Saadatmand, Fabiola Garcia Cortizo, Jakob Morgenstern, Alexandra Moraru, Sylvia Katz, Jutta Krebs-Haupenthal |
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Jazyk: | angličtina |
Rok vydání: | 2020 |
Předmět: |
Male
Proteomics 0301 basic medicine Aging Proteasome Endopeptidase Complex Ca2+/calmodulin-dependent kinase Michaelis–Menten kinetics General Biochemistry Genetics and Molecular Biology Cell Line Protein content 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Ubiquitin Neoplasms Detoxification Diabetes Mellitus post-translational modifications Animals Humans cellular biochemistry lcsh:QH301-705.5 Michaelis-Menten kinetics Mice Knockout biology Kinase phosphorylation Methylglyoxal Lactoylglutathione Lyase glyoxalase system Pyruvaldehyde Cell biology Mice Inbred C57BL Kinetics Phosphothreonine 030104 developmental biology chemistry lcsh:Biology (General) Inactivation Metabolic biology.protein Phosphorylation Calcium-Calmodulin-Dependent Protein Kinase Type 2 030217 neurology & neurosurgery Glyoxalase system |
Zdroj: | Cell Reports, Vol 32, Iss 12, Pp 108160-(2020) |
ISSN: | 2211-1247 |
Popis: | Summary: The glyoxalase system is a highly conserved and ubiquitously expressed enzyme system, which is responsible for the detoxification of methylglyoxal (MG), a spontaneous by-product of energy metabolism. This study is able to show that a phosphorylation of threonine-107 (T107) in the (rate-limiting) Glyoxalase 1 (Glo1) protein, mediated by Ca2+/calmodulin-dependent kinase II delta (CamKIIδ), is associated with elevated catalytic efficiency of Glo1 (lower KM; higher Vmax). Additionally, we observe proteasomal degradation of non-phosphorylated Glo1 via ubiquitination does occur more rapidly as compared with native Glo1. The absence of CamKIIδ is associated with poor detoxification capacity and decreased protein content of Glo1 in a murine CamKIIδ knockout model. Therefore, phosphorylation of T107 in the Glo1 protein by CamKIIδ is a quick and precise mechanism regulating Glo1 activity, which is experimentally linked to an altered Glo1 status in cancer, diabetes, and during aging. |
Databáze: | OpenAIRE |
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