De novo selection of oncogenes

Area of Science:

• Biochemistry
• Molecular Biology
• Protein Engineering

Background:

• Natural selection generates cellular proteins from existing ones, potentially limiting structural diversity.
• Evolutionary processes may discard or fail to develop novel, beneficial protein structures.

Purpose of the Study:

• To isolate novel, biologically active transmembrane proteins using a de novo selection approach.
• To generate proteins with unique structures and functions not found in nature.

Main Methods:

• A retroviral library of random hydrophobic amino acid sequences was screened in mouse cells.
• Genetic selection was employed to isolate functional transmembrane proteins.
• Focus formation in fibroblasts and tumor induction in mice were used as selection criteria.

Main Results:

• Four unique 29-amino acid transmembrane proteins were isolated, sharing no sequence homology with known proteins.
• The simplest isolated protein contained only seven different amino acids.
• These novel proteins transformed cells by activating the platelet-derived growth factor β receptor independently of its ligand.

Conclusions:

• De novo selection is a viable method for creating novel protein structures and functions.
• These findings offer potential for developing new research reagents and therapeutics.
• The study provides insights into cell biology, protein interactions, and potentially early life evolution.