Proteomic identification of proteins associated with the osmoregulatory transcription factor TonEBP/OREBP: functional effects of Hsp90 and PARP-1

Chen, Ye; Schnetz, Michael P.; Irarrázabal, Carlos E.; Shen, Rong-Fong; Williams, Chester K.; Burg, Maurice B.; Ferraris, Joan D.

doi:10.1152/ajprenal.00493.2005

Cited by 39 publications

(47 citation statements)

References 60 publications

(97 reference statements)

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“…As ddx17 has been co-purified with NFAT5 (Chen et al, 2007), we tested whether ddx17 and its paralog, ddx5, co-immunoprecipitate with NFAT5 in human MDA-MB-231 breast cancer cells. As shown on Figure 1a (left panel), FLAG-ddx17 protein was specifically detected after the immunoprecipitation of a Myc-NFAT5 protein.…”

Section: Resultsmentioning

confidence: 99%

Dual role of the ddx5/ddx17 RNA helicases in the control of the pro-migratory NFAT5 transcription factor

et al. 2012

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Ddx5 and ddx17 are two highly related RNA helicases involved in both transcription and splicing. These proteins coactivate transcription factors involved in cancer such as the estrogen receptor alpha, p53 and beta-catenin. Ddx5 and ddx17 are part of the splicing machinery and can modulate alternative splicing, the main mechanism increasing the proteome diversity. Alternative splicing also has a role in gene expression level regulation when it is coupled to the nonsensemediated mRNA decay (NMD) pathway. In this work, we report that ddx5 and ddx17 have a dual role in the control of the pro-migratory NFAT5 transcription factor. First, ddx5 and ddx17 act as transcriptional coactivators of NFAT5 and are required for activating NFAT5 target genes involved in tumor cell migration. Second, at the splicing level, ddx5 and ddx17 increase the inclusion of NFAT5 exon 5. As exon 5 contains a pre-mature translation termination codon, its inclusion leads to the regulation of NFAT5 mRNAs by the NMD pathway and to a decrease in NFAT5 protein level. Therefore, we demonstrated for the first time that a transcriptional coregulator can simultaneously regulate the transcriptional activity and alternative splicing of a transcription factor. This dual regulation, where ddx5 and ddx17 enhance the transcriptional activity of NFAT5 although reducing its protein expression level, suggests a critical role for ddx5 and ddx17 in tumor cell migration through the fine regulation of NFAT5 pathway.

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Section: Resultsmentioning

confidence: 99%

Dual role of the ddx5/ddx17 RNA helicases in the control of the pro-migratory NFAT5 transcription factor

et al. 2012

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“…As a member of the hnRNP H subfamily, this gene shares 78% identity with hnRNP F. Of interest, in addition to the involvement of hnRNP3 in early heat shock-induced splicing arrest (24), a very recent study has reported that several hnRNPs and small heterogeneous nuclear ribonucleoprotein were identified as part of a complex with HSP90, the regulatory and catalytic subunits of DNA-dependent protein kinase, various RNA helicases, poly (ADP-ribose) polymerase-1, and the osmotic regulatory transcription factor (TonEBP/OREBP) in human embryonic kidney cells (42). This suggests a role for the interaction of HSP90 and hnRNPs in regulating gene transcription.…”

Section: Discussionmentioning

confidence: 99%

Gene and Protein Expression Profiling of Human Ovarian Cancer Cells Treated with the Heat Shock Protein 90 Inhibitor 17-Allylamino-17-Demethoxygeldanamycin

Clarke²,

et al. 2007

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The promising antitumor activity of 17-allylamino-17-demethoxygeldanamycin (17AAG) results from inhibition of the molecular chaperone heat shock protein 90 (HSP90) and subsequent degradation of multiple oncogenic client proteins. Gene expression microarray and proteomic analysis were used to profile molecular changes in the A2780 human ovarian cancer cell line treated with 17AAG. Comparison of results with an inactive analogue and an alternative HSP90 inhibitor radicicol indicated that increased expression of HSP72, HSC70, HSP27, HSP47, and HSP90B at the mRNA level were on-target effects of 17AAG. HSP27 protein levels were increased in tumor biopsies following treatment of patients with 17AAG. A group of MYC-regulated mRNAs was decreased by 17AAG. Of particular interest and novelty were changes in expression of chromatin-associated proteins. Expression of the heterochromatin protein 1 was increased, and expression of the histone acetyltransferase 1 and the histone arginine methyltransferase PRMT5 was decreased by 17AAG. PRMT5 was shown to be a novel HSP90-binding partner and potential client protein. Cellular protein acetylation was reduced by 17AAG, which was shown to have an antagonistic interaction on cell proliferation with the histone deacetylase inhibitor trichostatin A. This mRNA and protein expression analysis has provided new insights into the complex molecular pharmacology of 17AAG and suggested new genes and proteins that may be involved in response to the drug or be potential biomarkers of drug action. [Cancer Res 2007;67(7):3239-53]

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“…NFAT5 was also documented to be part of a bulky complex, which consists of several other partners, such as catalytic subunit of PKA [9], ATM [10], RNA Helicase A [11], TAZ [12], FSP27 [13], β-catenin [14], AP-1 [15], HSP-90 [16] and PARP1 [16]. Among these interacting partners, PARP1, an inhibitor of transcriptional activity of NFAT5 [16], catalyzes poly (ADP-ribosyl)ation of proteins, as well as plays a role in DNA repair mechanism using NAD + as cofactor [17]. In this regard, PARP1 has also been shown to influence several intracellular pathways, reciprocally with a deacetylase, SIRT1 due to utilization of common cofactor NAD + [18][19][20].…”

Section: Introductionmentioning

confidence: 99%

SIRT1 contributes to aldose reductase expression through modulating NFAT5 under osmotic stress: In vitro and in silico insights

Timuçin

Bodur

Başağa

2015

Cellular Signalling

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Proteomic identification of proteins associated with the osmoregulatory transcription factor TonEBP/OREBP: functional effects of Hsp90 and PARP-1

Abstract: Chen Y, Schnetz MP, Irarrazabal CE, Shen RF, Williams CK, Burg MB, Ferraris JD. Proteomic identification of proteins associated with the osmoregulatory transcription factor TonEBP/OREBP: functional effects of Hsp90 and PARP-1.

Cited by 39 publications

References 60 publications

Dual role of the ddx5/ddx17 RNA helicases in the control of the pro-migratory NFAT5 transcription factor

Dual role of the ddx5/ddx17 RNA helicases in the control of the pro-migratory NFAT5 transcription factor

Gene and Protein Expression Profiling of Human Ovarian Cancer Cells Treated with the Heat Shock Protein 90 Inhibitor 17-Allylamino-17-Demethoxygeldanamycin

SIRT1 contributes to aldose reductase expression through modulating NFAT5 under osmotic stress: In vitro and in silico insights

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