p38 is essential for the assembly and stability of macromolecular tRNA synthetase complex: implications for its physiological significance.
Mammalian tRNA synthetases form a macromolecular complex with three nonenzyme factors: p43, p38, and p18. Here we introduced a mutation within the mouse p38 gene to understand its functional significance for the formation of the multi-tRNA synthetase complex. The complex was completely disintegrated by the deficiency of p38. In addition, the protein levels and catalytic activities of the component enzymes and cofactors were severely decreased. A partial truncation of the p38 polypeptide separated the associated components into different subdomains. The mutant mice showed lethality within 2 days of birth. Thus, this work provides the first evidence, to our knowledge, that p38 is essential for the structural integrity of the multi-tRNA synthetase complex and mouse viability.
Kim
Jin Young
JY
National Creative Research Initiatives Center for ARS Network, College of Pharmacy, Seoul National University, San 56-1, Shillim-dong, Kwanak-gu, Seoul 151-746, Korea.
Kang
Young-Sun
YS
Lee
Joong-Won
JW
Kim
Hyoung June
HJ
Ahn
Young Ha
YH
Park
Heonyong
H
Ko
Young-Gyu
YG
Kim
Sunghoon
S
D000604:Amino Acyl-tRNA Synthetases / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D005347:Fibroblasts / Q000378:metabolism; D017353:Gene Deletion; D006801:Humans; D007700:Kinetics; D051379:Mice; D016297:Mutagenesis, Site-Directed; D021122:Protein Subunits; D011994:Recombinant Proteins / Q000378:metabolism; D014158:Transcription, Genetic; D014162:Transfection
D021122:Protein Subunits; D011994:Recombinant Proteins; D000604:Amino Acyl-tRNA Synthetases