GEO Logo
   NCBI > GEO > Accession DisplayHelp Not logged in | LoginHelp
GEO help: Mouse over screen elements for information.
Series GSE14339 Query DataSets for GSE14339
Status Public on Jun 15, 2009
Title Stress-dependent CHIP/Daxx interaction suppresses the p53 apoptotic program
Organism Mus musculus
Experiment type Expression profiling by array
Summary 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
Overall design We utilized a “sample x reference” 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).
Contributor(s) McDonough H, Charles PC, Hilliard EG, Qian S, Min J, Portbury A, Cyr DM, Patterson C
Citation(s) 19465479
Submission date Jan 08, 2009
Last update date Jan 12, 2017
Contact name Jonathan C Schisler
Phone 919-843-8708
Organization name The University of North Carolina at Chapel Hill
Department McAllister Heart Institute
Lab Schisler Lab
Street address MBRB, Rm 2340C
City Chapel Hill
State/province NC
ZIP/Postal code 27599-7126
Country USA
Platforms (1)
GPL7202 Agilent-014868 Whole Mouse Genome Microarray 4x44K G4122F (Probe Name version)
Samples (24)
GSM358716 Wildtype_30m_Baseline_rep1
GSM358717 Wildtype_30m_Baseline_rep2
GSM358718 Wildtype_30m_Baseline_rep3
BioProject PRJNA111521

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE14339_RAW.tar 305.9 Mb (http)(custom) TAR (of TXT)
Processed data included within Sample table

| NLM | NIH | GEO Help | Disclaimer | Accessibility |
NCBI Home NCBI Search NCBI SiteMap