Compositions and Methods for Inhibiting Tumor Cells by Inhibiting the Transcription Factor ATF5

Abstract

The present invention relates to methods for treating and/or preventing tumors and/or promoting apoptosis in a neoplastic cell comprising contacting the neoplastic cell with an cell-penetrating dominant-negative ATF5 (“CP-d/n-ATF5”), wherein the CP-d/n-ATF5 is capable of inhibiting ATF5 function and/or activity.

1 - 8 . (canceled) 
     
     
         9 . A dominant-negative ATF5 molecule consisting essentially of a sequence that is at least 60% identical to LEGECQGLEARNRELKERAESV (SEQ ID NO: 26). 
     
     
         10 . The dominant-negative ATF5 molecule of  claim 9 , further comprising a cell-penetrating peptide, wherein the dominant-negative ATF5 molecule is linked to an amino terminus or a carboxy terminus of the cell-penetrating peptide. 
     
     
         11 . The dominant-negative ATF5 molecule of  claim 10 , wherein the cell-penetrating peptide is selected from the group consisting of penetratin 1, transportan, pIS1, Tat(48-60), pVEC, MAP, and MTS. 
     
     
         12 . The dominant-negative ATF5 molecule of  claim 11 , wherein the penetratin 1 comprises a sequence that is at least 70% identical to RQIKIWFQNRRMKWKK (SEQ ID NO: 34). 
     
     
         13 . The dominant-negative ATF5 molecule of  claim 9 , further comprising from 1 to 24 additional C-terminal ATF5 leucine zipper residues. 
     
     
         14 . A composition comprising the dominant-negative ATF5 molecule of any of  claims 9 - 13  and a pharmaceutically acceptable carrier. 
     
     
         15 . A method of decreasing viability of a neoplastic cell, comprising contacting the neoplastic cell with the dominant-negative ATF5 molecule of any of  claims 9 - 13 .