title: The proline-rich region of mouse p53 influences transactivation and apoptosis but is largely dispensable for these functions.
abstract: The N-terminal proline-rich domain of human p53 has been shown to be important for the induction of apoptosis. However, the corresponding region in mouse and other species is not highly conserved and has been less well studied. In this paper, we have characterized mutants with deletions in this region of mouse p53. Our results demonstrate that deletions in the proline-rich domain have varying effects on function ranging from no effect to severe impairment of cell death activity, depending on precisely which residues are deleted. We also show that the mutants differ in their ability to transactivate different p53 target promoters. Although we have been able to obtain mutants selectively impaired for apoptosis, our data are not generally consistent with this region being a functional domain. The data are more consistent with the interpretation that the region influences function by altering local protein structure which may affect promoter discrimination.
authors.affiliation: Department of Pathology, Dunedin School of Medicine, University of Otago, Box 913, Dunedin, New Zealand. sara.edwards@stonebow.otago.ac.nz
authors.forename: Sara J
authors.initials: SJ
authors.lastname: Edwards
authors.forename: Lynne
authors.initials: L
authors.lastname: Hananeia
authors.forename: Michael R
authors.initials: MR
authors.lastname: Eccles
authors.forename: You Fang
authors.initials: YF
authors.lastname: Zhang
authors.forename: Antony W
authors.initials: AW
authors.lastname: Braithwaite
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D016923:Cell Death / Q000235:genetics; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000235:genetics / Q000378:metabolism; D005347:Fibroblasts; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009154:Mutation; D011392:Proline; D017434:Protein Structure, Tertiary; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D013329:Structure-Activity Relationship; D015533:Transcriptional Activation / Q000502:physiology*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*; D051028:bcl-2-Associated X Protein
chemical_list: C493956:CDKN1A protein, human; C493957:Cdkn1a protein, mouse; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; D011392:Proline