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High throughput gene expression data from MDA-MB-231 breast cancer cell lines with DAXX Knockdown, DAXX WT overexpression (OE), and DAXX SUMO interacting motif mutant (DSM) overexpression (DSM OW)

ABSTRACT: DAXX, originally discovered as a context-dependent regulator of cell death or survival. Emerging evidence suggests that DAXX has an oncogenic role in diverse cancer types. However, the molecular mechanisms underlying DAXX's oncogenic function remain to be defined. We used high throughput Illumina sequencing to analyze genes that were differentially expressed upon DAXX knockdown or DAXX OE or DSM OE.

ORGANISM(S): Homo sapiens

PROVIDER: GSE192420 | GEO | 2021/12/24

REPOSITORIES: GEO

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Project description:Our previous studies have implicated CHIP as a co-chaperone/ubiquitin ligase, whose activities yield protection against stress-induced apoptotic events. In this report, we demonstrate a stress-dependent interaction between CHIP (carboxyl terminus of Hsp70-interacting protein) and Daxx, death domain-associated protein. This interaction interferes with the stress-dependent association of HIPK2 with Daxx, blocking phosphorylation of serine 46 in p53 and inhibiting the p53-dependent apoptotic program. Microarray analysis confirmed suppression of the p53-dependent transcriptional portrait in CHIP (+/+) but not in CHIP (-/-) heat shocked MEFs. The interaction between CHIP and Daxx results in ubiquitination of Daxx which is then partitioned to an insoluble compartment of the cell. In vitro ubiquitination of Daxx by CHIP revealed that Ub chain formation utilizes non canonical lysine linkages associated with resistance to proteasomal degradation. CHIP's ubiquitination of Daxx utilizes lysines 630 and 631 and competes with the cell's sumoylation machinery at these residues. These studies implicate CHIP as a stress-dependent regulator of Daxx that counters Daxx's pro-apoptotic influence in the cell. By abrogating p53-dependent apoptotic pathways and by ubiquitination competitive with Daxx sumoylation, CHIP integrates the cell's proteotoxic stress response with cell cycle pathways that influence cell survival. Keywords: p53, apoptosis, cell stress, ubiquitination We utilized a âsample x referenceâ experimental design strategy in which RNA extracted from mouse embryonic fibroblasts was hybridized to the microarray slide in the presence of labeled Universal Mouse Reference RNA (UMRR, Stratagene, LaJolla, CA). A total of 24 RNA samples were used in this analysis. Briefly, five hundred nanograms of total RNA were used for gene expression profiling following reverse transcription and T-7 polymerase-mediated amplification/labeling with Cyanine-5 CTP. Labeled subject cRNA was co-hybridized to Agilent G4112F Whole Mouse Genome 4x44K oligonucleotide arrays with equimolar amounts of Cyanine-3 labeled UHRR. Slides were hybridized, washed, and scanned on an Axon 4000b microarray scanner. The data were processed using Feature Extaction software (Agilent, Santa Clara, CA).

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High throughput gene expression data from MDA-MB-231 breast cancer cell lines with DAXX Knockdown, DAXX WT overexpression (OE), and DAXX SUMO interacting motif mutant (DSM) overexpression (DSM OW)

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