期刊
CELL SYSTEMS
卷 12, 期 7, 页码 716-+出版社
CELL PRESS
DOI: 10.1016/j.cels.2021.05.002
关键词
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资金
- UCSD
- NIH [R01HG009285, RO1CA222826, RO1GM123313, U54CA209891]
- NHLBI [T32 HL 105373]
- NSF [DGE-1650112]
Gene fragments derived from structural domains mediating physical interactions can modulate biological functions. By developing lentiviral overexpression libraries of peptides tiling oncogenes, researchers identified peptides that selectively reduced cellular proliferation. Coupling cell-penetrating motifs to these peptides enabled drug-like function, with potential for rapid mapping of bioactive protein domains.
Gene fragments derived from structural domains mediating physical interactions can modulate biological functions. Utilizing this, we developed lentiviral overexpression libraries of peptides comprehensively tiling high-confidence cancer driver genes. Toward inhibiting cancer growth, we assayed similar to 66,000 peptides, tiling 65 cancer drivers and 579 mutant alleles. Pooled fitness screens in two breast cancer cell lines revealed peptides, which selectively reduced cellular proliferation, implicating oncogenic protein domains important for cell fitness. Coupling of cell-penetrating motifs to these peptides enabled drug-like function, with peptides derived from EGFR and RAF1 inhibiting cell growth at IC50s of 27-63 mM. We anticipate that this peptide-tiling (PepTile) approach will enable rapid de novo mapping of bioactive protein domains and associated interfering peptides.
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