Chimeric peptides for the regulation of GTPases

摘要

Chimeric peptides or fusion proteins are disclosed that include a RhoGAP activity domain and at least one specificity domain that targets a specific Rho protein. The fusion proteins can be used to inhibit any GTPase activity within a cell. The fusion proteins are particularly advantageous for the treatment of cancer. The present invention generally relates to chimeric peptides capable of regulating GTPases, and more particularly, to methods of targeting individual GTPases by using GTPase-activating proteins. Such proteins may be used for the treatment of cancers and other GTPase-related diseases. This invention relates to nucleic acid molecules and the encoded GTPase activating proteins, and variants thereof, and to the use of these molecules in the characterization, diagnosis, prevention, and treatment of cell signaling, immune, and cell proliferative disorders, particularly cancer. Disclosed herein are compounds and methods for regulating transcription of a selected gene.

主权项

1. A method of treating a disease related to up-regulation of GTPase activity in a mammal, comprising administering to the mammal a composition in an amount effective to reduce the GTPase activity, wherein the composition comprises: (i) a chimeric polypeptide comprising a guanosine-triphosphatase-activating protein (GAP) activity domain consisting of amino acids 1248 to 1513 of SEQ ID NO: 2 or a fragment thereof having GAP activity, and at least one targeting domain comprising the amino acid sequence of SEQ ID NO: 16 or a fragment thereof which targets at least one specific guanosine triphosphatase (GTPase) protein; and (ii) a pharmaceutically acceptable carrier.