Site-specific cleavage of acetoacetyl-CoA synthetase by legumain. 2016

Shinya Hasegawa, and Daiki Inoue, and Masahiro Yamasaki, and Chuan Li, and Masahiko Imai, and Noriko Takahashi, and Tetsuya Fukui
Department of Health Chemistry, Hoshi University, Shinagawa, Tokyo, Japan.

Acetoacetyl-CoA synthetase (AACS) is a ketone body-utilizing enzyme and is responsible for the synthesis of cholesterol and fatty acids. We have previously shown that AACS is cleaved by legumain, a lysosomal asparaginyl endopeptidase. In this study, we attempted to determine the cleavage site of AACS. Mutagenesis analysis of AACS revealed that Asn547 is the specific cleavage site of AACS in mouse livers. The cleaved form of AACS (1-547) lost the ability to convert acetoacetate to acetoacetyl-CoA. Moreover, hydrodynamics-based gene transduction showed that overexpression of AACS (1-547) increases the protein expression of caveolin-1, the principal component of the caveolae. These results suggest that cleavage of AACS by legumain is critical for the regulation of enzymatic activity and results in gain-of-function changes.

UI MeSH Term Description Entries
D008297 Male Males
D008822 Mice, Transgenic Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN. Transgenic Mice,Founder Mice, Transgenic,Mouse, Founder, Transgenic,Mouse, Transgenic,Mice, Transgenic Founder,Transgenic Founder Mice,Transgenic Mouse
D002478 Cells, Cultured Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others. Cultured Cells,Cell, Cultured,Cultured Cell
D003066 Coenzyme A Ligases Enzymes that catalyze the formation of acyl-CoA derivatives. EC 6.2.1. Acyl CoA Synthetase,Acyl CoA Synthetases,Acyl Coenzyme A Synthetase,Acyl Coenzyme A Synthetases,Coenzyme A Ligase,Coenzyme A Synthetase,Coenzyme A Synthetases,Acid-Thiol Ligases,Co A Ligases,A Ligase, Coenzyme,A Synthetase, Coenzyme,Acid Thiol Ligases,CoA Synthetase, Acyl,CoA Synthetases, Acyl,Ligase, Coenzyme A,Ligases, Acid-Thiol,Ligases, Co A,Ligases, Coenzyme A,Synthetase, Acyl CoA,Synthetase, Coenzyme A,Synthetases, Acyl CoA,Synthetases, Coenzyme A
D003546 Cysteine Endopeptidases ENDOPEPTIDASES which have a cysteine involved in the catalytic process. This group of enzymes is inactivated by CYSTEINE PROTEINASE INHIBITORS such as CYSTATINS and SULFHYDRYL REAGENTS.
D004789 Enzyme Activation Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1, activation by ions (activators); 2, activation by cofactors (coenzymes); and 3, conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme. Activation, Enzyme,Activations, Enzyme,Enzyme Activations
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001665 Binding Sites The parts of a macromolecule that directly participate in its specific combination with another molecule. Combining Site,Binding Site,Combining Sites,Site, Binding,Site, Combining,Sites, Binding,Sites, Combining
D013379 Substrate Specificity A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts. Specificities, Substrate,Specificity, Substrate,Substrate Specificities

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