4RP6: Structure Of The Amyloid-forming Segment Ltiitle From P53 (residues 252-258)

Citation:
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.
PDB ID: 4RP6Download
MMDB ID: 135306
PDB Deposition Date: 2014/10/29
Updated in MMDB: 2016/01
Experimental Method:
x-ray diffraction
Resolution: 1.7  Å
Source Organism:
Similar Structures:
Biological Unit for 4RP6: hexameric; determined by author
Molecular Components in 4RP6
Label Count Molecule
Proteins (6 molecules)
6
Ltiitle Heptapeptide Segment From P53(Gene symbol: TP53)
Molecule annotation
* Click molecule labels to explore molecular sequence information.

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