Inactivation of Ras function by allele-specific peptide aptamers.
One challenge facing biology is the elucidation of the function of the estimated 30 000 human genes and their polymorphic variants. Reagents that affect the activity of specific genes will be useful in the dissection of cellular regulatory networks. Here, as a test case, we used a two-bait two-hybrid system to identify peptide aptamers that distinguish allelic forms of H-Ras. Some of these anti-Ras aptamters inhibit the interaction of oncogenic Ras with c-Raf1 in vitro, and abolish EGF-stimulated activation of c-Raf1 in vivo. These experiments show that the inactivation of protein function by peptide aptamers represents a viable approach to the understanding and control of signaling pathways and oncogenic missense alleles.
Xu
C Wilson
CW
Molecular Pharmacology and Chemistry Program, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA. w-xu@ski.mskcc.org
Luo
Zhijun
Z
D000483:Alleles; D000595:Amino Acid Sequence; D004815:Epidermal Growth Factor / Q000494:pharmacology; D011905:Genes, ras / Q000502:physiology*; D008969:Molecular Sequence Data; D010455:Peptides / Q000494:pharmacology*; D019908:Proto-Oncogene Proteins c-raf / Q000378:metabolism; D020798:Two-Hybrid System Techniques
D010455:Peptides; D004815:Epidermal Growth Factor; D019908:Proto-Oncogene Proteins c-raf