title: p28, an anionic cell-penetrating peptide, increases the activity of wild type and mutated p53 without altering its conformation.
abstract: p28, a cell penetrating peptide, binds to the DNA binding domain (DBD) of p53, inducing a post-translational increase in intracellular levels of wild type and mutant p53 activating pathways that inhibit cancer cell proliferation at G2/M. Cancer cells respond to p28 with an increase in p53 activity, except when mutations either alter DNA contact or completely unfold the DBD. The increase in p53 activity is accompanied by a significant reduction in the level of the E3 ligase COP1, with no alteration in p53 conformation. This suggests p28 can activate p53 over a wide range of conformational mutations by inhibiting the binding of COP1 to p53.
authors: Department of Surgery, Division of Surgical Oncology, University of Illinois at Chicago College of Medicine, 840 South Wood Street, Suite 618, Chicago, Illinois 60612, United States.
authors: Tohru
authors: T
authors: Yamada
authors: Tapas K
authors: TK
authors: Das Gupta
authors: Craig W
authors: CW
authors: Beattie
mesh_terms: D002460:Cell Line; D045744:Cell Line, Tumor; D057846:Cell-Penetrating Peptides / Q000494:pharmacology*; D006801:Humans; D056004:Molecular Dynamics Simulation; D009154:Mutation; D011485:Protein Binding; D011487:Protein Conformation / Q000187:drug effects; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016159:Tumor Suppressor Protein p53 / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
chemical_list: D057846:Cell-Penetrating Peptides; D016159:Tumor Suppressor Protein p53; D044767:Ubiquitin-Protein Ligases