TP53 truncating mutations are common in human tumors and are thought to give rise to p53-null alleles. Here, we show that TP53 exon-6 truncating mutations occur at higher than expected frequencies and produce proteins that lack canonical p53 tumor suppressor activities but promote cancer cell proliferation, survival, and metastasis. Functionally and molecularly, these p53 mutants resemble the naturally occurring alternative p53 splice variant, p53-psi. Accordingly, these mutants can localize to the mitochondria where they promote tumor phenotypes by binding and activating the mitochondria inner pore permeability regulator, Cyclophilin D (CypD). Together, our studies reveal that TP53 exon-6 truncating mutations, contrary to current beliefs, act beyond p53 loss to promote tumorigenesis, and could inform the development of strategies to target cancers driven by these prevalent mutations.
Pubmed ID: 27759562 RIS Download
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View all literature mentionsMus musculus with name C57BL/6J from IMSR.
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View all literature mentionsThis monoclonal targets Cyclophilin F antibody [E11AE12BD4]
View all literature mentionsThis polyclonal targets p44/42 MAPK (Erk1/2)
View all literature mentionsThis polyclonal targets Cleaved PARP (Asp214) (Human Specific)
View all literature mentionsThis polyclonal targets Tom20 (FL-145)
View all literature mentionsThis monoclonal targets Ras-GAP
View all literature mentionsThis monoclonal targets α-Tubulin
View all literature mentionsThis monoclonal targets p53 (Ab-6) (Pantropic) Mouse mAb (DO-1)
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View all literature mentionsCell line NCI-H2126 is a Cancer cell line with a species of origin Homo sapiens (Human)
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View all literature mentionsCell line B16-F1 is a Cancer cell line with a species of origin Mus musculus (Mouse)
View all literature mentionsCell line HOP-62 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line HCC1937 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line NCI-H1299 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line AU565 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line A-549 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line DMS 114 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line HEK293T is a Transformed cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line MCF-7 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line SW684 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line MCF-7 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line NCI-H2126 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line AU565 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsNetwork of ftp and web servers around world that store identical, up to date, versions of code and documentation for R. Package archive network for R programming language.
View all literature mentionsStatistical analysis software that combines scientific graphing, comprehensive curve fitting (nonlinear regression), understandable statistics, and data organization. Designed for biological research applications in pharmacology, physiology, and other biological fields for data analysis, hypothesis testing, and modeling.
View all literature mentionsThis monoclonal targets FLAG
View all literature mentionsThis monoclonal targets Cyclophilin F antibody [E11AE12BD4]
View all literature mentionsThis polyclonal targets Cleaved PARP (Asp214) (Human Specific)
View all literature mentionsThis polyclonal targets p44/42 MAPK (Erk1/2)
View all literature mentionsThis monoclonal targets Ras-GAP
View all literature mentionsThis polyclonal targets Tom20 (FL-145)
View all literature mentionsThis monoclonal targets α-Tubulin
View all literature mentionsThis monoclonal targets p53 (Ab-6) (Pantropic) Mouse mAb (DO-1)
View all literature mentionsCell line DMS 114 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line SW684 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line HEK293T is a Transformed cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line Calu-6 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line B16-F1 is a Cancer cell line with a species of origin Mus musculus (Mouse)
View all literature mentionsCell line HCC1937 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line HOP-62 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line NCI-H1299 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line A-549 is a Cancer cell line with a species of origin Homo sapiens (Human)
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