Abstract
In the preceding paper we found from molecular dynamics calculations that the structure of the ras-binding domain (RBD) 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 RBD 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 p2l. 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.
Similar content being viewed by others
REFERENCES
Amar, S., Glozman, A., Chung, D. L., Adler, V., Ronai, Z., Friedman, F. K., Robinson, R., Brandt-Rauf, P. W., Yamaizumi, Z., and Pincus, M. R. (1997). Cancer Chemother. Pharmacol., submitted.
Aroca, P., Mahadevan, D., and Santos, E. (1996). Oncogene 13, 1839–1846.
Birchmeier, C., Broek, D., and Wigler, M. (1985). Cell 43, 615–621.
Bokoch, G. M. (1993). Biochem. J. 289, 17–24.
Chen, J. M., Manolatos, S., Brandt-Rauf, P. W., Monaco, R., and Pincus, M. R. (1996). J. Protein Chem. 15, 511–518.
Chen, J. M., Manolatos, S., Monaco, R., Brandt-Rauf, P. W., Friedman, F. K., and Pincus, M. R. (1997). J. Protein Chem., this issue.
Chung, D. L., Brandt-Rauf, P. W., Murphy, R. B., Nishimura, S., Yamaizumi, Z., Weinstein, I. B., and Pincus, M. R. (1991). Anticancer Res. 11, 1373–1378.
Chung, D. L., Joran, A., Friedman, F. K., Robinson, R. R., Brandt-Rauf, P. W., Weinstein, I. B., Ronai, Z. A., Baskin, L., Dykes, D. C., Murphy, R. B., Nishimura, S., Yamaizumi, Z., and Pincus, M. R. (1992). Exp. Cell Res. 203, 329–335.
Deshpande, A. K., and Kung, H.-F. (1987). Mol. Cell. Biol. 7, 1285–1288.
Haspel, J., Dykes, D. C., Friedman, F. K., Robinson, R., Chung, D., Ronai, Z., Brandt-Rauf, P. W., Baskin, L., Weinstein, I. B., Nishimura, S., Yamaizumi, Z., Singh, G., Murphy, R. B., and Pincus, M. R. (1992). Med. Sci. Res. 20, 809–811.
Karin, M. (1995). J. Biol. Chem. 270, 16483–16486.
Medema, R. H., Wubbolts, R., and Bos, J. L. (1991). Mol. Cell. Biol. 11, 5963–5967.
Miura, K., Inouye, Y., Nakamori, H., Iwai, S., Ohtsuka, E., Ikehara, M., Noguchi, S., and Nishimura, S. (1986). Jpn. J. Cancer Res. (Gann) 77, 45–51.
Pincus, M. R., Chung, D. L., Dykes, D. C., Brandt-Rauf, P. W., Weinstein, I. B., Yamaizumi, Z., and Nishimura, S. (1992). Ann. Clin. Lab. Sci. 22, 323–342.
Stacey, D. W., Feig, L. A., and Gibbs, J. B. (1991). Mol. Cell. Biol. 11, 4053–4064.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Chung, D., Amar, S., Glozman, A. et al. 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. J Protein Chem 16, 631–635 (1997). https://doi.org/10.1023/A:1026374908495
Published:
Issue Date:
DOI: https://doi.org/10.1023/A:1026374908495