title: The DNA-binding and transcription-activation abilities of p53 are necessary but not sufficient for its antiproliferation function.
abstract: Normal p53 protein suppresses cell proliferation and ras oncogene-induced cell transformation. Missense mutations in the middle conserved conformational domain of p53 decrease its antiproliferation function. In this work, we studied the requirement of the NH2- and COOH-terminal regions of p53 in its antiproliferation function using two independent assays, growth of chronic myelogenous leukemia K562 cells on methylcellulose semisolid medium and ras oncogene-induced focus formation of rat fibroblast cells (Rat-1). We found that deletion of 80 or 159 amino acids from the NH2-terminus and deletion of 67 amino acids from the COOH-terminus of p53 drastically reduced the antiproliferation function of p53. However, the COOH-terminal deletion mutant is capable of binding to a p53 DNA-binding element, p53CON (GGACATGCCCGGGCATGTCC), and of activating p53CON-mediated transcription. These results suggest that p53' abilities to bind p53CON and activate transcription are not sufficient for its antiproliferation function and that p53CON-regulated genes may not be growth suppressive.
authors.affiliation: Department of Hematology, University of Texas M.D. Anderson Cancer Center, Houston 77030.
authors.forename: W
authors.initials: W
authors.lastname: Zhang
authors.forename: G S
authors.initials: GS
authors.lastname: Randhawa
authors.forename: X Y
authors.initials: XY
authors.lastname: Guo
authors.forename: A B
authors.initials: AB
authors.lastname: Deisseroth
mesh_terms: D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002455:Cell Division / Q000502:physiology*; D004247:DNA / Q000378:metabolism*; D005347:Fibroblasts; D006801:Humans; D004915:Leukemia, Erythroblastic, Acute; D008969:Molecular Sequence Data; D011485:Protein Binding; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D017384:Sequence Deletion; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000737:chemistry / Q000502:physiology*
chemical_list: D011993:Recombinant Fusion Proteins; D016159:Tumor Suppressor Protein p53; D004247:DNA