Role of pescadillo in the transformation and immortalization of mammalian cells

Maiorana, Arianna; Tu, Xiao; Cheng, Guanjun; Baserga, Renato

doi:10.1038/sj.onc.1207916

Cited by 35 publications

(41 citation statements)

References 57 publications

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“…Confocal Microscopy-Confocal microscopy studies followed the same procedures described in detail in previous reports from our laboratory (16,17,29). The antibodies used are indicated in the appropriate figures.…”

Section: Cells and Cellmentioning

confidence: 99%

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Functional Significance of Type 1 Insulin-like Growth Factor-mediated Nuclear Translocation of the Insulin Receptor Substrate-1 and β-Catenin

Chen

Sun

et al. 2005

Journal of Biological Chemistry

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108

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Previous work has shown that the transcriptional regulator ␤-catenin can translocate to the nuclei when cells are stimulated with the type 1 insulin-like growth factor (IGF-1). We show by immunocoprecipitation and by confocal microscopy that ␤-catenin binds to and co-localizes with the insulin receptor substrate-1 (IRS-1), a docking protein for both the insulin and the IGF-1 receptors. IRS-1 is required for IGF-1-mediated nuclear translocation of ␤-catenin, resulting in the activation of the ␤-catenin target genes. IGF-1-mediated nuclear translocation of ␤-catenin is facilitated by the nuclear translocation of IRS-1. Both IRS-1 and ␤-catenin are recruited to the cyclin D1 promoter, an established target for ␤-catenin, but only IRS-1 is recruited to the ribosomal DNA (rDNA) promoter. UBF proteins (known to interact with both IRS-1 and ␤-catenin) are also detectable in the cyclin D1 and rDNA promoters. These results indicate that IRS-1 (activated by the IGF-1 receptor) is one of several proteins that regulate the subcellular localization and activity of ␤-catenin. The ability of IRS-1 to localize to both RNA polymerase II (with ␤-catenin) and RNA polymerase I-regulated promoters suggest an explanation for the effect of IRS-1 on both cell growth in size and cell proliferation. This possibility is supported by the demonstration that enforced nuclear localization of IRS-1 causes nuclear translocation of ␤-catenin and transformation of normal mouse embryo fibroblasts (colony formation in soft agar).The important roles played by ␤-catenin in adhesion, cancer, and development and its connections to Wnt and APC have been discussed in recent reviews (1-3). Briefly, there is usually a large pool of ␤-catenin in the cytoplasm, where it is targeted for destruction by phosphorylation of the N terminus (2, 4). Under certain circumstances, for instance Wnt signaling, ␤-catenin is stabilized and transferred to the nuclei where it binds members of the family of T-cell factor/lymphoid enhancer factors (Tcf/Lef) and activates transcription of target genes (5, 6). Among genes regulated by ␤-catenin are c-myc (7) and cyclin D1 (8, 9), which encode critical cell-cycle progression proteins (a list of target genes can be found at www.stanford.edu/ϳrnusse/ pathways/targets.html). Recently, we found by our modified TAPtag technique that the insulin receptor substrate-1 (IRS-1) 1 interacts in the nuclei with ␤-catenin (10). IRS-1, a docking protein for both the IGF-1 and insulin receptors, sends a strong mitogenic, anti-apoptotic, and anti-differentiation signal (11,12). Overexpression or ectopic expression of IRS-1 can cause cell transformation, including the ability of cells to form colonies in soft agar and tumors in mice (13). Under certain circumstances, IRS-1 translocates to the nuclei (14 -16) where it interacts with nuclear proteins, including viral oncoproteins (14, 17), the upstream binding factor 1 (UBF1) (15,16), and the estrogen receptor (18).IGFs are known to cause translocation of ␤-catenin to the nuclei, where it activates ...

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Section: Cells and Cellmentioning

confidence: 99%

“…Colony Formation in Soft Agar-The methodology previously described was followed (29). Briefly, to compare anchorage-independent growth of different cell lines, cells were plated at 2 ϫ 10 3 in essential modified Eagle's medium containing 10% fetal bovine serum (plus or minus IGF-1) and 0.2% agarose (with 0.4% agarose underlay).…”

Section: Cells and Cellmentioning

confidence: 99%

Functional Significance of Type 1 Insulin-like Growth Factor-mediated Nuclear Translocation of the Insulin Receptor Substrate-1 and β-Catenin

Chen

Sun

et al. 2005

Journal of Biological Chemistry

Self Cite

108

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“…Furthermore, knockdown of PES1 slows down the proliferation of breast cancer cells. PES1 stimulates cell proliferation by promoting both ribosome biogenesis and cell cycle progression (11)(12)(13). Now Cheng et al hypothesize that PES1 induces breast tumor growth by regulating steroid hormone signaling through control of the turnover of both ERα and ERβ.…”

Section: Pes1 Governs the Er Subtypesmentioning

confidence: 99%

Targeting PES1 for restoring the ERα/ERβ ratio in breast cancer

Thomas¹,

Gustafsson²

2012

J. Clin. Invest.

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Alteration of the ERα/ERβ balance is a critical step in breast cancer development and progression, and selective restoration of the activity of estrogen receptors has been proposed as one of the major therapeutic approaches for breast cancer. In this issue of JCI, Cheng et al. show that, by differentially modulating the stability of ERα and ERβ, PES1 increases the ERα/ERβ ratio and triggers breast tumor growth. These findings highlight PES1 as a potential target for the treatment of breast cancer. Conflict of interest:The authors have declared that no conflict of interest exists.Citation for this article: J Clin Invest.

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“…In the nucleus, IRS-1 has been shown to bind to b-catenin and facilitate activation of Tcf/Lef transcription of target genes such as the cell cycle progression genes Cyclin D1 or c-Myc (Morelli et al, 2004;Chen et al, 2005;Wu et al, 2008). Moreover, nuclear IRS-1 directly binds to upstream binding factor 1 (UBF-1) and Pescadillo which are involved in ribosome biogenesis (Tu et al, 2002;Sun et al, 2003;Maiorana et al, 2004;Prisco et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

Xenopus laevis insulin receptor substrate IRS‐1 is important for eye development

Bugner

Aurhammer

Kühl

2011

Developmental Dynamics

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Extracellular signal transduction into cells through ligand-activated receptor tyrosine kinases, such as insulin-like growth factor-1 (IGF-1) receptor (IGF-1R) and insulin receptor (IR) is required for normal embryonic growth and development. The major mediators of IR and IGF-1R are adaptor proteins of the insulin receptor substrate family, the best characterized member of which is IRS-1. Insulin receptor substrate IRS-1 has been shown to influence cell and body size and to interfere with differentiation. We have isolated IRS-1 from Xenopus laevis embryos and analyzed for the first time its spatial and temporal expression pattern during embryogenesis. We found that Xenopus IRS-1 is expressed maternally and constantly during embryogenesis. It is predominantly found in neural tissue at different stages. Furthermore, knock down of IRS-1 in neural tissue by specific antisense morpholino oligonucleotides (MO) resulted in abnormal eye formation accompanied by reduction of the eye-specific marker genes Rx1 and Pax6 and a decreased cell proliferation. Developmental Dynamics 240:1705-1715,

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Role of pescadillo in the transformation and immortalization of mammalian cells

Cited by 35 publications

References 57 publications

Functional Significance of Type 1 Insulin-like Growth Factor-mediated Nuclear Translocation of the Insulin Receptor Substrate-1 and β-Catenin

Functional Significance of Type 1 Insulin-like Growth Factor-mediated Nuclear Translocation of the Insulin Receptor Substrate-1 and β-Catenin

Targeting PES1 for restoring the ERα/ERβ ratio in breast cancer

Xenopus laevis insulin receptor substrate IRS‐1 is important for eye development

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