Pag, a Putative Tumor Suppressor, Interacts with the Myc Box II Domain of c-Myc and Selectively Alters Its Biological Function and Target Gene Expression

Mu, Zhao Mei; Yin, Xiao Ying; Prochownik, Edward V.

doi:10.1074/jbc.m206066200

Cited by 122 publications

(125 citation statements)

References 55 publications

(79 reference statements)

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“…Most important, however, is that Prx1 potently abrogates c-Myc-mediated transformation in vitro. 27 Indeed, subsequent work in prx1 knockout mice did indeed demonstrate higher levels of ROS in several tissues as well as a predisposition to cancer, thus confirming Prx1's role as a tumor suppressor. 28 In an independently derived prx1 knockout strain, we showed that c-Myc, while not expressed at noticeably higher levels than in control cells, did nonetheless appear to be functionally de-regulated since primary prx -/-MEFs could be transformed by oncogenic ras alone, as opposed to the usual necessary combination of c-Myc+ras.…”

Section: The "Oncogene From Hell" Reduxmentioning

confidence: 79%

“…Work from our laboratory has shown that peroxiredoxin 1 (Prx1), a widely expressed scavenger of ROS, 26 interacts with the transcriptional regulatory domain of c-Myc, specifically with the critical 15-20 amino acid "Myc Box II" region that is essential for transformation. 27 The consequences of this interaction are complex, with certain aspects of the c-Myc phenotype being suppressed by Prx1 while others are enhanced. Most important, however, is that Prx1 potently abrogates c-Myc-mediated transformation in vitro.…”

Section: The "Oncogene From Hell" Reduxmentioning

confidence: 99%

See 1 more Smart Citation

The Ever Expanding Role for c-Myc in Promoting Genomic Instability

Prochownik¹,

Li²

2007

Cell Cycle

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Section: The "Oncogene From Hell" Reduxmentioning

confidence: 79%

Section: The "Oncogene From Hell" Reduxmentioning

confidence: 99%

The Ever Expanding Role for c-Myc in Promoting Genomic Instability

Prochownik¹,

Li²

2007

Cell Cycle

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“…Upon peroxidatic Cys oxidation, 2‐Cys PRDX1 is structurally converted from a peroxidase enzyme to a molecular chaperone under stress conditions 9, 10. In addition to its peroxidase and chaperone functions, PRDX1 could also enhance natural killer cell cytotoxicity and suppress oncogenic proteins such as c‐Myc and c‐Abl 11, 12, 13. Recent studies have shown that abnormal expression of PRDX1 has been observed in several human cancers, including breast, oesophageal, lung and prostate cancers 14, 15, 16, 17.…”

Section: Introductionmentioning

confidence: 99%

Peroxiredoxin 1 – an antioxidant enzyme in cancer

Ding

Fan

2016

J Cellular Molecular Medi

165

131

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Peroxiredoxins (PRDXs), a ubiquitous family of redox‐regulating proteins, are reported of potential to eliminate various reactive oxygen species (ROS). As a major member of the antioxidant enzymes, PRDX1 can become easily over‐oxidized on its catalytically active cysteine induced by a variety of stimuli in vitro and in vivo. In nucleus, oligomeric PRDX1 directly associates with p53 or transcription factors such as c‐Myc, NF‐κB and AR, and thus affects their bioactivities upon gene regulation, which in turn induces or suppresses cell death. Additionally, PRDX1 in cytoplasm has anti‐apoptotic potential through direct or indirect interactions with several ROS‐dependent (redox regulation) effectors, including ASK1, p66Shc, GSTpi/JNK and c‐Abl kinase. PRDX1 is proven to be a versatile molecule regulating cell growth, differentiation and apoptosis. Recent studies have found that PRDX1 and/or PRDX1‐regulated ROS‐dependent signalling pathways play an important role in the progression and metastasis of human tumours, particularly in breast, oesophageal and lung cancers. In this paper, we review the structure, effector functions of PRDX1, its role in cancer and the pivotal role of ROS in anticancer treatment.

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“…We next evaluated each yeast strain to determine whether it could be propagated on medium lacking histidine and adenine, and if it could express b-galactosidase, as these properties would be indicative of protein-protein association (Langlands et al, 1997;Mu et al, 2002). The latter measurement could also be used to quantify the relative strength of any such interactions (Langlands et al, 1997).…”

Section: Onzin Overexpression Promotes Growth Survival and Transformentioning

confidence: 99%

“…Viable cell counts were then performed daily using trypan blue exclusion as described previously (Nesbit et al, 1998;Landay et al, 2000). Ongoing apoptosis was documented by showing the presence of cells with a subdiploid DNA content and by the TUNEL assay as described previously (Mu et al, 2002; data not shown). (b) Phase-contrast micrographs of representative Rat1a clones 7 days after the removal of serum or 3 days after the addition of VP-16 or adriamycin.…”

Section: Onzin Overexpression Promotes Growth Survival and Transformentioning

confidence: 99%

Onzin, a c-Myc-repressed target, promotes survival and transformation by modulating the Akt–Mdm2–p53 pathway

et al. 2005

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The c-Myc oncoprotein is a general transcription factor whose target genes dictate the c-Myc phenotype. One such target of c-Myc, 'onzin', is normally expressed at high levels in myeloid cells and is dramatically downregulated in response to c-Myc overexpression. We show here that short hairpin interfering RNA-mediated knockdown of endogenous onzin results in a reduced growth rate and a proapoptotic phenotype. In contrast, onzin overexpression in fibroblasts is associated with an increased growth rate, resistance to apoptotic stimuli, loss of the G2/M checkpoint, and tumorigenic conversion. Onzin-overexpressing cells fail to induce p53 in response to apoptotic stimuli and contain higher levels of the active, phosphorylated forms of Akt1 and, more strikingly, of Mdm2. Using yeast two-hybrid and coimmunoprecipitation assays, we show that onzin directly interacts with both proteins. Green fluorescent protein tagging also confirms directly that Akt1 and Mdm2 colocalize with onzin, although the precise subcellular distribution of each protein is dependent on its relative abundance. Collectively, our results identify onzin as a novel regulator of several p53-dependent aspects of the c-Myc phenotype via its dramatic effect on Mdm2. This is reminiscent of the c-Mycp19 ARF -| Mdm2 pathway and might function as a complementary arm to ensure the proper cellular response to oncogenic and/or apoptotic stimuli.

show abstract

Pag, a Putative Tumor Suppressor, Interacts with the Myc Box II Domain of c-Myc and Selectively Alters Its Biological Function and Target Gene Expression

Cited by 122 publications

References 55 publications

The Ever Expanding Role for c-Myc in Promoting Genomic Instability

The Ever Expanding Role for c-Myc in Promoting Genomic Instability

Peroxiredoxin 1 – an antioxidant enzyme in cancer

Onzin, a c-Myc-repressed target, promotes survival and transformation by modulating the Akt–Mdm2–p53 pathway

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