Inhibition of oncogenic and activated wild-type ras-p21 protein-induced oocyte maturation by peptides from the ras-binding domain of the raf-p74 protein, identified from molecular dynamics calculations

被引:22
作者
Chung, D
Amar, S
Glozman, A
Chen, JM
Friedman, FK
Robinson, R
Monaco, R
BrandtRauf, P
Yamaizumi, Z
Pincus, MR
机构
[1] VET AFFAIRS MED CTR,DEPT PATHOL & LAB MED,BROOKLYN,NY 11209
[2] SUNY HLTH SCI CTR,DEPT PATHOL,BROOKLYN,NY 11203
[3] LONG ISL UNIV,DEPT CHEM,BROOKLYN,NY 11201
[4] LONG ISL UNIV,DEPT BIOL,BROOKLYN,NY 11201
[5] DUPONT CO INC,STINE HASKELL RES CTR,DEPT AGR PROD,NEWARK,DE 19714
[6] NIH,MOL CARCINOGENESIS LAB,BETHESDA,MD 20892
[7] NYU,DEPT BIOL,NEW YORK,NY 10003
[8] COLUMBIA UNIV COLL PHYS & SURG,DIV ENVIRONM SCI,NEW YORK,NY 10032
[9] NATL CANC INST,TOKYO,JAPAN
来源
JOURNAL OF PROTEIN CHEMISTRY | 1997年 / 16卷 / 06期
关键词
ras-binding domain of raf; raf effector domain peptides; peptide inhibition of oocyte maturation; molecular dynamics;
D O I
10.1023/A:1026374908495
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
In the preceding paper we found from molecular dynamics calculations that the structure of the ras-binding domain (RED) of raf changes predominantly in three regions depending upon whether it binds to ras-p21 protein or to its inhibitor protein, rap-1A, These three regions of the RED involve residues from the protein-protein interaction interface, e.g., between residues 60 and 72, residues 97-110, and 111-121. Since the rap-1A-RBD complex is inactive, these three regions are implicated in ras-p21-induced activation of raf. We have therefore co-microinjected peptides corresponding to these three regions, 62-76, 97-110, and 111-121, into oocytes with oncogenic p21 and microinjected them into oocytes incubated in in insulin, which activates normal p21. All three peptides, but not a control peptide, strongly inhibit both oncogenic p21- and insulin-induced oocyte maturation, These findings corroborate our conclusions from the theoretical results that these three regions constitute raf effector domains. Since the 97-110 peptide is the strongest inhibitor of oncogenic p21, while the 111-121 peptide is the strongest inhibitor of insulin-induced oocyte maturation, the possibility exists that oncogenic and activated normal p21 proteins interact differently with the RBD of raf.
引用
收藏
页码:631 / 635
页数:5
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