4RP6
Structure of the amyloid-forming segment LTIITLE from p53 (residues 252-258)
Summary for 4RP6
| Entry DOI | 10.2210/pdb4rp6/pdb |
| Related | 4RP7 |
| Descriptor | LTIITLE heptapeptide segment from p53 (2 entities in total) |
| Functional Keywords | p53, amyloid, fibril, amyloid-like protofibril, p53 aggregates, polymer, transcription factor, oncogene, cancer, p53 mutant, protein fibril |
| Biological source | Homo sapiens (human) |
| Cellular location | Cytoplasm. Isoform 1: Nucleus. Isoform 2: Nucleus. Isoform 3: Nucleus. Isoform 4: Nucleus. Isoform 7: Nucleus. Isoform 8: Nucleus. Isoform 9: Cytoplasm: P04637 |
| Total number of polymer chains | 1 |
| Total formula weight | 801.97 |
| Authors | Soriaga, A.B.,Soragni, A.,Eisenberg, D. (deposition date: 2014-10-29, release date: 2016-01-13, Last modification date: 2024-02-28) |
| Primary citation | Soragni, A.,Janzen, D.M.,Johnson, L.M.,Lindgren, A.G.,Thai-Quynh Nguyen, A.,Tiourin, E.,Soriaga, A.B.,Lu, J.,Jiang, L.,Faull, K.F.,Pellegrini, M.,Memarzadeh, S.,Eisenberg, D.S. A Designed Inhibitor of p53 Aggregation Rescues p53 Tumor Suppression in Ovarian Carcinomas. Cancer Cell, 29:90-103, 2016 Cited by PubMed Abstract: Half of all human cancers lose p53 function by missense mutations, with an unknown fraction of these containing p53 in a self-aggregated amyloid-like state. Here we show that a cell-penetrating peptide, ReACp53, designed to inhibit p53 amyloid formation, rescues p53 function in cancer cell lines and in organoids derived from high-grade serous ovarian carcinomas (HGSOC), an aggressive cancer characterized by ubiquitous p53 mutations. Rescued p53 behaves similarly to its wild-type counterpart in regulating target genes, reducing cell proliferation and increasing cell death. Intraperitoneal administration decreases tumor proliferation and shrinks xenografts in vivo. Our data show the effectiveness of targeting a specific aggregation defect of p53 and its potential applicability to HGSOCs. PubMed: 26748848DOI: 10.1016/j.ccell.2015.12.002 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.703 Å) |
Structure validation
Download full validation report
