Heterogeneous Nuclear Ribonucleoprotein K Enhances Insulin-induced Expression of Mitochondrial UCP2 Protein

Ostrowski, Jerzy; Klimek-Tomczak, Karolina; Mikula, Michał; Schullery, Daniel S.; Bomsztyk, Karol

doi:10.1074/jbc.m406753200

Cited by 31 publications

(39 citation statements)

References 70 publications

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“…K protein is upregulated in malignant cells (Dejgaard et al, 1994;Mandal et al, 2001;Li et al, 2004), and it regulates the expression of genes involved in mitogenic responses, indicating that it has a direct role in cancerogenesis (Michelotti et al, 1995(Michelotti et al, , 1996Ostrowski et al, 2004). We have shown that following mitogenic stimulation, K protein is recruited to gene loci known to be upregulated in malignant states, including c-myc .…”

mentioning

confidence: 85%

“…As K protein is upregulated in tumour cells (Dejgaard et al, 1994;Mandal et al, 2001;Li et al, 2004) and modulates the expression of genes involved in mitogenic responses (Michelotti et al, 1995(Michelotti et al, , 1996Mandal et al, 2001;Ostrowski et al, 2004), altering its properties and introduction of a new phosphorylation site could make K protein either more or less conducive for the cellular processes that lead to tumorigenic state. If so, identification of this novel tumour-associated K protein isoform may prove to be a useful diagnostic, prognostic and/or therapeutic indicator.…”

Section: P<005mentioning

confidence: 99%

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Editing of hnRNP K protein mRNA in colorectal adenocarcinoma and surrounding mucosa

et al. 2006

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The heterogeneous nuclear ribonucleoprotein K (hnRNP K) protein is an RNA-binding protein involved in many processes that compose gene expression. K protein is upregulated in the malignant processes and has been shown to modulate the expression of genes involved in mitogenic responses and tumorigenesis. To explore the possibility that there are alternative isoforms of K protein expressed in colon cancer, we amplified and sequenced K protein mRNA that was isolated from colorectal cancers as well as from normal tissues surrounding the tumours. Sequencing revealed a single G-to-A base substitution at position 274 that was found in tumours and surrounding mucosa, but not in individuals that had no colorectal tumour. This substitution most likely reflects an RNA editing event because it was not found in the corresponding genomic DNAs. Sequencing of RNA from normal colonic mucosa of patients with prior resection of colorectal cancer revealed only the wild-type K protein transcript, indicating that G274A isoform is tumour related. To our knowledge, this is the first example of an RNA editing event in cancer and its surrounding tissue, a finding that may offer a new diagnostic and treatment marker.

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confidence: 85%

Section: P<005mentioning

confidence: 99%

Editing of hnRNP K protein mRNA in colorectal adenocarcinoma and surrounding mucosa

et al. 2006

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“…mitochondria It has been established that insulin increases levels of mitochondrial hnRNP K protein [9]. To obtain more information on the mitochondrial topology of hnRNP K protein and its potential import mechanisms, we investigated the mitochondrial transport of hnRNP K protein using an in vitro mitochondrial import system with the protein synthesized in vitro by coupled transcription-translation.…”

Section: Insulin Increases Import Of Hnrnp K Protein Intomentioning

confidence: 99%

“…Murine hnRNP K protein cDNA was inserted into pAdTrack vector, and HTC-IR cells were transfected as previously described [9].…”

Section: Adenovirus Construction and Infectionmentioning

confidence: 99%

“…Mitochondria were purified from cells by differential centrifugation [9] using Cytosol Extraction Buffer from the BioVision Kit (BioVision Inc.). Freshly prepared mitochondria were suspended in an isotonic sucrose buffer (0.25 M sucrose, 1 mM ethylenediaminetetraacetic acid (EDTA), 10 mM Tris-HCl, pH 7.4) and then were further purified by centrifugation through a 1.0/1.5 M discontinuous sucrose gradient [10].…”

Section: Hnrnp K Protein Import Into Mitochondriamentioning

confidence: 99%

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The diverse involvement of heterogeneous nuclear ribonucleoprotein K in mitochondrial response to insulin

Dzwonek¹,

Mikula²,

Ostrowski³

2006

FEBS Letters

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Heterogeneous nuclear ribonucleoprotein K (hnRNP K protein) is an RNA/DNA-binding protein that acts in several compartments, including mitochondria. It integrates cellular signaling cascades with multiple processes of gene expression mechanisms. Our studies demonstrate that: (1) insulin activates the import of hnRNP K protein into mitochondria in vitro and in vivo; (2) overexpression of hnRNP K protein modulates insulin-activated mitochondrial gene expression; and (3) insulin treatment stimulates binding of hnRNP K protein to mitochondrial DNA. Based on these and our previously reported results we conclude that hnRNP K protein may be a mediator of mitochondrial response to insulin.

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Proteomic analysis of increased Parkin expression and its interactants provides evidence for a role in modulation of mitochondrial function

Davison¹,

Pennington²,

Hung³

et al. 2009

Proteomics

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Parkin is an ubiquitin-protein ligase (E3), mutations of which cause juvenile onset - autosomal recessive Parkinson's disease, and result in reduced enzymic activity. In contrast, increased levels are protective against mitochondrial dysfunction and neurodegeneration, the mechanism of which is largely unknown. In this study, 2-DE and MS proteomic techniques were utilised to investigate the effects of increased Parkin levels on protein expression in whole cell lysates using in an inducible Parkin expression system in HEK293 cells, and also to isolate potential interactants of Parkin using tandem affinity purification and MS. Nine proteins were significantly differentially expressed (+/-2-fold change; p<0.05) using 2-DE analysis. MS revealed the identity of these proteins to be ACAT2, HNRNPK, HSPD1, PGK1, PRDX6, VCL, VIM, TPI1, and IMPDH2. The first seven of these were reduced in expression. Western blot analysis confirmed the reduction in one of these proteins (HNRNPK), and that its levels were dependent on 26S proteasomal activity. Tandem affinity purification/MS revealed 14 potential interactants of Parkin; CKB, DBT, HSPD1, HSPA9, LRPPRC, NDUFS2, PRDX6, SLC25A5, TPI1, UCHL1, UQCRC1, VCL, YWHAZ, YWHAE. Nine of these are directly involved in mitochondrial energy metabolism and glycolysis; four were also identified in the 2-DE study (HSP60, PRDX6, TPI1, and VCL). This study provides further evidence for a role for Parkin in regulating mitochondrial activity within cells.

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Heterogeneous Nuclear Ribonucleoprotein K Enhances Insulin-induced Expression of Mitochondrial UCP2 Protein

Cited by 31 publications

References 70 publications

Editing of hnRNP K protein mRNA in colorectal adenocarcinoma and surrounding mucosa

Editing of hnRNP K protein mRNA in colorectal adenocarcinoma and surrounding mucosa

The diverse involvement of heterogeneous nuclear ribonucleoprotein K in mitochondrial response to insulin

Proteomic analysis of increased Parkin expression and its interactants provides evidence for a role in modulation of mitochondrial function

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