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
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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