Part of: Cancer Cell Line Encyclopedia (CCLE) project.
Part of: ENCODE project common cell types; tier 2.
Part of: JFCR39 cancer cell line panel.
Part of: KuDOS 95 cell line panel.
Part of: MD Anderson Cell Lines Project.
Part of: Naval Biosciences Laboratory (NBL) collection (transferred to ATCC in 1982).
Part of: NCI60 cancer cell line panel.
Doubling time: 22 hours (PubMed=25984343); 22.9 hours (DTP); ~40 hours (DSMZ).
Microsatellite instability: Stable (MSS) (PubMed=12661003; Sanger).
Omics: Acetylation analysis by proteomics.
Omics: Deep antibody staining analysis.
Omics: Deep exome analysis.
Omics: Deep phosphoproteome analysis.
Omics: Deep membrane proteome analysis.
Omics: Deep proteome analysis.
Omics: Deep RNAseq analysis.
Omics: DNA methylation analysis.
Omics: H3K4me3 ChIP-seq epigenome analysis.
Omics: H3K9ac ChIP-seq epigenome analysis.
Omics: Protein expression by reverse-phase protein arrays.
Omics: Proteome analysis by 2D-DE/MS.
Omics: shRNA library screening.
Omics: SNP array analysis.
Omics: Transcriptome analysis.
Omics: Virome analysis using proteomics.
Misspelling: 'A594' in PubMed=18227028.
Misspelling: 'A59' in PubMed=16354588.
Discontinued: ATCC; CRL-7909.
The 2013-2016 outbreak of Ebola virus (EBOV) in West Africa was the largest recorded. It began following the cross-species transmission of EBOV from an animal reservoir, most likely bats, into humans, with phylogenetic analysis revealing the co-circulation of several viral lineages. We hypothesized that this prolonged human circulation led to genomic changes that increased viral transmissibility in humans. We generated a synthetic glycoprotein (GP) construct based on the earliest reported isolate and introduced amino acid substitutions that defined viral lineages. Mutant GPs were used to generate a panel of pseudoviruses, which were used to infect different human and bat cell lines. These data revealed that specific amino acid substitutions in the EBOV GP have increased tropism for human cells, while reducing tropism for bat cells. Such increased infectivity may have enhanced the ability of EBOV to transmit among humans and contributed to the wide geographic distribution of some viral lineages.
Blockade of lysosomal calcium release due to lysosomal lipid accumulation has been shown to inhibit mTORC1 signaling. However, the mechanism by which lysosomal calcium regulates mTORC1 has remained undefined. Herein we report that proper lysosomal calcium release through the calcium channel TRPML1 is required for mTORC1 activation. TRPML1 depletion inhibits mTORC1 activity, while overexpression or pharmacologic activation of TRPML1 has the opposite effect. Lysosomal calcium activates mTORC1 by inducing association of calmodulin (CaM) with mTOR. Blocking the interaction between mTOR and CaM by antagonists of CaM significantly inhibits mTORC1 activity. Moreover, CaM is capable of stimulating the kinase activity of mTORC1 in a calcium-dependent manner in vitro. These results reveal that mTOR is a new type of CaM-dependent kinase, and TRPML1, lysosomal calcium and CaM play essential regulatory roles in the mTORC1 signaling pathway.
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.
Increasing evidence highlights the important roles of microRNAs in mediating p53's tumor suppression functions. Here, we report miR-139-5p as another new p53 microRNA target. p53 induced the transcription of miR-139-5p, which in turn suppressed the protein levels of phosphodiesterase 4D (PDE4D), an oncogenic protein involved in multiple tumor promoting processes. Knockdown of p53 reversed these effects. Also, overexpression of miR-139-5p decreased PDE4D levels and increased cellular cAMP levels, leading to BIM-mediated cell growth arrest. Furthermore, our analysis of human colorectal tumor specimens revealed significant inverse correlation between the expression of miR-139-5p and that of PDE4D. Finally, overexpression of miR-139-5p suppressed the growth of xenograft tumors, accompanied by decrease in PDE4D and increase in BIM. These results demonstrate that p53 inactivates oncogenic PDE4D by inducing the expression of miR-139-5p.
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