title: Turning a scorpion toxin into an antitumor miniprotein.
abstract: The oncoproteins MDM2 and MDMX negatively regulate the activity and stability of the tumor suppressor protein p53 and are important molecular targets for anticancer therapy. Grafting four residues of p53 critical for MDM2/MDMX binding to the N-terminal alpha-helix of BmBKTx1, a scorpion toxin isolated from the venom of the Asian scorpion Buthus martensi Karsch, converts the miniature protein into an effective inhibitor of p53 interactions with MDM2 and MDMX. Additional mutations enable the 27-residue miniprotein inhibitor to traverse the cell membrane and selectively kill tumor cells in a p53 dependent manner.
authors.affiliation: Institute of Human Virology, University of Maryland School of Medicine, 725 West Lombard Street, Baltimore, Maryland 21201, USA.
authors.forename: Chong
authors.initials: C
authors.lastname: Li
authors.forename: Min
authors.initials: M
authors.lastname: Liu
authors.forename: Juahdi
authors.initials: J
authors.lastname: Monbo
authors.forename: Guozhang
authors.initials: G
authors.lastname: Zou
authors.forename: Changqing
authors.initials: C
authors.lastname: Li
authors.forename: Weirong
authors.initials: W
authors.lastname: Yuan
authors.forename: Davide
authors.initials: D
authors.lastname: Zella
authors.forename: Wei-Yue
authors.initials: WY
authors.lastname: Lu
authors.forename: Wuyuan
authors.initials: W
authors.lastname: Lu
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry*; D008958:Models, Molecular; D017434:Protein Structure, Tertiary; D012604:Scorpion Venoms / Q000737:chemistry*; D012605:Scorpions / Q000737:chemistry*; D040681:Structural Homology, Protein
chemical_list: D000970:Antineoplastic Agents; D012604:Scorpion Venoms
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