Moll, Ute M.

[["dc.bibliographiccitation.issue","6"],["dc.bibliographiccitation.journal","Cancers"],["dc.bibliographiccitation.volume","10"],["dc.contributor.author","Schulz-Heddergott, Ramona"],["dc.contributor.author","Moll, Ute M."],["dc.date.accessioned","2019-07-09T11:45:42Z"],["dc.date.available","2019-07-09T11:45:42Z"],["dc.date.issued","2018"],["dc.description.abstract","p53 missense mutant alleles are present in nearly 40% of all human tumors. Such mutated alleles generate aberrant proteins that not only lose their tumor-suppressive functions but also frequently act as driver oncogenes, which promote malignant progression, invasion, metastasis, and chemoresistance, leading to reduced survival in patients and mice. Notably, these oncogenic gain-of-function (GOF) missense mutant p53 proteins (mutp53) are constitutively and tumor-specific stabilised. This stabilisation is one key pre-requisite for their GOF and is largely due to mutp53 protection from the E3 ubiquitin ligases Mdm2 and CHIP by the HSP90/HDAC6 chaperone machinery. Recent mouse models provide convincing evidence that tumors with highly stabilized GOF mutp53 proteins depend on them for growth, maintenance, and metastasis, thus creating exploitable tumor-specific vulnerabilities that markedly increase lifespan if intercepted. This identifies mutp53 as a promising cancer-specific drug target. This review discusses direct mutp53 protein-targeting drug strategies that are currently being developed at various preclinical levels."],["dc.identifier.doi","10.3390/cancers10060188"],["dc.identifier.pmid","29875343"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/15288"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/59288"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.publisher","MDPI"],["dc.relation.eissn","2072-6694"],["dc.relation.issn","2072-6694"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.subject.ddc","300"],["dc.subject.ddc","320"],["dc.title","Gain-of-Function (GOF) Mutant p53 as Actionable Therapeutic Target"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]