Retinoic acid mediates degradation of IRS-1 by the ubiquitin–proteasome pathway, via a PKC-dependant mechanism

Rincón, Sonia V. del; Guo, Qi; Morelli, Catia; Shiu, Hoi-Ying; Surmacz, Eva; Miller, Wilson H.

doi:10.1038/sj.onc.1208104

Cited by 58 publications

(29 citation statements)

References 48 publications

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“…IRS-1 per se is also known to be a strong mitogen and to inhibit differentiation (3)(4)(5). Downregulation of IRS-1 (by either antisense or small interfering RNA) abrogates the transformed phenotype (6)(7)(8). IRS-1 plays a major role in the regulation of cell size (2,4,37), and deletion of IRS-1 genes in mice (38) or Drosophila (39) causes a 50% reduction in body size.…”

Section: Discussionmentioning

confidence: 99%

“…IRS-1 expression is often increased in human cancer (3), and overexpression or ectopic expression of IRS-1 causes cell transformation, including the ability to form colonies in soft agar and tumors in mice (4,5). When IRS-1 levels are decreased by experimental procedures (antisense or small interfering RNA), cancer cells lose their transformed phenotype (6)(7)(8). IRS-1 levels are low or even absent in differentiating cells (2,9,10), and ectopic expression of IRS-1 inhibits differentiation (4,10).…”

Section: Introductionmentioning

confidence: 99%

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Insulin Receptor Substrate-1 Regulates the Transformed Phenotype of BT-20 Human Mammary Cancer Cells

Dalmızrak

Chen

et al. 2007

Cancer Research

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Although originating from a human breast cancer, BT-20 cells do not form colonies in soft agar. BT-20 cells do not express insulin receptor substrate-1 (IRS-1), which is known to promote both normal and abnormal growth and to inhibit differentiation. Stable expression of IRS-1 confers to BT-20 cells the ability to form colonies in soft agar. BT-20 cells form tumors in xenografts in mice, but the size of tumors is twice as large when the cells express IRS-1. The increased transformed phenotype is characterized by occupancy of the rDNA and cyclin D1 promoters by IRS-1 and the activation of the cyclin D1, c-myc, and rDNA promoters. In addition, the retinoblastoma protein, which is detectable in the rDNA promoter of quiescent BT-20/IRS-1 cells, is replaced by IRS-1 after insulinlike growth factor-I stimulation. Our results indicate that in BT-20 human mammary cancer cells, expression of IRS-1 activates promoters involved in cell growth and cell proliferation, resulting in a more transformed phenotype. Targeting of IRS-1 could be effective in inhibiting the proliferation of mammary cancer cells. [Cancer Res 2007;67(5):2124-30]

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Insulin Receptor Substrate-1 Regulates the Transformed Phenotype of BT-20 Human Mammary Cancer Cells

Dalmızrak

Chen

et al. 2007

Cancer Research

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“…15,[23][24][25][26][27][28][29][30] Conversely, downregulation of IRS-1 (by antisense or siRNA) reverses the transformed phenotype. [30][31][32][33] One intriguing aspect of IRS-1 downregulation is that cells that do not express IRS-1 survive, although they have a tendency to differentiate (see above). A similar situation occurs with the IGF-IR.…”

Section: Discussionmentioning

confidence: 99%

Growth inhibition by microRNAs that target the insulin receptor substrate-1

Rocca

Shi²,

Badin³

et al. 2009

Cell Cycle

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We have examined several microRNAs (miRs) indicated by the databases as targeting the signaling pathway of the type-1 insulin-like growth factor receptor (IGF-IR). Most of the miRs tested had multiple targets, as expected, leading to cell death. However, miR145 seemed to affect its tumor suppressor activity largely by downregulating the docking protein of the IGF-IR, the insulin receptor substrate-1 (IRS-1). These results suggest that, despite the many targets provided by the databases, in some cases a single target can be predominant in determining the end results.

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“…This last property of IRS-1 is the focus of the present communication. When IRS-1 levels are decreased by experimental procedures, cancer cells lose their transformed phenotype (D'Ambrosio et al, 1995;del Rincon et al, 2004). Over-expression or ectopic expression of IRS-1 causes cell transformation, including the ability to form colonies in soft agar and tumors in mice (Cristofanelli et al, 2000;Valentinis et al, 2000;DeAngelis et al, 2006;Dearth et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

Nuclear insulin receptor substrate-1 activates promoters of cell cycle progression genes

Chen

Baserga

2007

Oncogene

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The insulin receptor substrate-1 (IRS-1) is a docking protein of the insulin-like growth factor-1 (IGF-1) receptor and of the insulin receptor. IRS-1 sends a strong mitogenic, anti-apoptotic signal and plays an important role in cell transformation and cancer. IRS-1 translocates to nuclei of cells, where it increases the activity of the rDNA, c-myc and cyclin D1 promoters. We show, by chromatin immunoprecipitation, occupancy by IRS-1 of the same promoters. Both promoter activation and promoter occupancy are IGF-1-dependent. In cells that respond to IGF-1 but in which IRS-1 does not translocate to nuclei, promoter occupancy is absent and promoter activation is absent or much reduced. Transcriptional activation of c-myc and cyclin D1 promoters by nuclear IRS-1 does not occur with a mutant, inactive IRS-1 protein (deletion of the phosphotyrosine-binding domain, PTB) and does not require PI3-kinase activity. Taken together, these results indicate a novel mechanism by which nuclear IRS-1 activates cell cycle genes.

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Retinoic acid mediates degradation of IRS-1 by the ubiquitin–proteasome pathway, via a PKC-dependant mechanism

Cited by 58 publications

References 48 publications

Insulin Receptor Substrate-1 Regulates the Transformed Phenotype of BT-20 Human Mammary Cancer Cells

Insulin Receptor Substrate-1 Regulates the Transformed Phenotype of BT-20 Human Mammary Cancer Cells

Growth inhibition by microRNAs that target the insulin receptor substrate-1

Nuclear insulin receptor substrate-1 activates promoters of cell cycle progression genes

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