4RP6

Structure of the amyloid-forming segment LTIITLE from p53 (residues 252-258)

4RP6 の概要

• エントリーDOI: 10.2210/pdb4rp6/pdb
• 関連するPDBエントリー: 4RP7
• 分子名称: LTIITLE heptapeptide segment from p53 (2 entities in total)
• 機能のキーワード: p53, amyloid, fibril, amyloid-like protofibril, p53 aggregates, polymer, transcription factor, oncogene, cancer, p53 mutant, protein fibril
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cytoplasm. Isoform 1: Nucleus. Isoform 2: Nucleus. Isoform 3: Nucleus. Isoform 4: Nucleus. Isoform 7: Nucleus. Isoform 8: Nucleus. Isoform 9: Cytoplasm: P04637
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 801.97

構造登録者

Soriaga, A.B.,Soragni, A.,Eisenberg, D. (登録日: 2014-10-29, 公開日: 2016-01-13, 最終更新日: 2024-02-28)

主引用文献

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

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: 26748848
DOI: 10.1016/j.ccell.2015.12.002

実験手法

X-RAY DIFFRACTION (1.703 Å)