| Project/Area Number |
63044090
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| Research Category |
Grant-in-Aid for international Scientific Research
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| Allocation Type | Single-year Grants |
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| Section | Joint Research |
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| Research Institution | Osaka University |
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Principal Investigator |
TSUNASAWA Susumu Institute for Protein Research, Osaka University, Associate Professor, 蛋白質研究所, 助教授 (30029962)
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| Co-Investigator(Kenkyū-buntansha) |
BULGAC Ellena University of Rochester, Assistant Professor, 医学部, 準教授
STERNGLANZ Rolf New York State University, Professor, 医学部, 教授
MOERSCHELL Richard University of Rochester, Assistant Professor, 医学部, 準教授
DUMONT Mark University of Rochester, Associate Professor, 医学部, 助教授
SHERMAN Fred University of Rochester, Professor, 医学部, 教授
KATO Ikunoshin Biotechonolgy Research Laboratories, Takara Shuzo Co., Head, バイオ研究所, 所長
YAMADA Michiyuki Institute for Protein Research, Osaka University, Associate Professor, 蛋白質研究所, 助教授 (10076995)
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| Project Period (FY) |
1988 – 1990
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| Project Status |
Completed (Fiscal Year 1990)
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| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 1990: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 1989: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 1988: ¥800,000 (Direct Cost: ¥800,000)
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| Keywords | Processing / Acetylation / Methionine aminopeptidase / Post-translational modification / Acetyltransferase / 開始メチオニン |
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| Research Abstract |
A large part of cellular proteins are in a dynamic state of turnover. Protein breakdown is responsible for essential cellular functions such as the modulation of the levels of key enzymes and regulatory proteins and removal of abnormal proteins. For the half-lives of individual proteins it has been reported that N-terminal amino acid is an important factor.
To study for the role of N-terminal amino acid on regulation for breakdown of cellular proteins, we have investigated to elucidate the rules of N-terminal processing observed in newly synthesized proteins by using various iso-1-cytochrome c mutants altered at their N-terminal region as a model system, and to isolate the related enzymes.
The results suggest that initiator methionine (Met) is completely removed from penultimate residue having radii of glynation on 1, 29 A or less, and that of those newly, appeared amino acids at least glycine, serine and alanine are acetylated depending on some structural characterization. Furthermore, of the retained N-terminal methionine residues, the proteins having both Met-Asp- and Met-Glu sequences are also acetylated. From these results it has been thus estimated that at least the following three enzymes are conjugated in N-terminal processing of proteins. The first enzyme is a methionine aminopeptidase (MAP), which acts on removal of initiator methionine, and the second and the third are N-acetyltransferases with different specificities as suggested above (NAT1 : for glycine, alanine and serine as the N-terminal amino acid ; nat2 : for methionine followed by acidic residues). The isolation of these three enzymes are now undergoing using saccharomyces cerevisiae as the materials.
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