Regulation of IGF Gene Expression

Holthuizen, P. Elly; Steenbergh, P. H.; Sussenbach, J.S.

doi:10.1007/978-1-59259-712-3_3

Cited by 6 publications

(5 citation statements)

References 137 publications

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“…On the other hand, IGFs are widespread peptides known to be present in lower and higher eukaryotes [10,[30][31][32]. In animals, these highly conserved peptides are known to play important roles in promoting basic biological processes such as cell cycle progression, cell growth, survival and cell differentiation [8,31,33]. Similar peptides have also been found in plants (Figures 1-4) [19,20], suggesting that they have a very early evolutionary origin [18] ; however, their biological activity has not been investigated in these organisms.…”

Section: Discussionmentioning

confidence: 99%

A maize insulin-like growth factor signals to a transduction pathway that regulates protein synthesis in maize

Flores

Aguilar

Cruz

et al. 2001

Biochemical Journal

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Insulin and insulin-like growth factors (IGFs) are well-characterized regulators in higher eukaryotic cells that control biological processes such as cell growth and survival, and selective translation of mRNAs. This research presents the purification of a 20kDa protein, isolated from maize tissue, with IGF activity. The protein was purified from 48h-germinated maize embryonic axes by G-50 Sephadex fractionation followed by affinity chromatography through a bovine insulin antibody–Sepharose column. This protein proved to significantly speed up maize germination and seedling growth. At the molecular level, Zea mays IGF (ZmIGF) enhanced phosphorylation of S6 ribosomal protein (rp) on the 40S ribosomal subunit, in a similar way as observed when bovine insulin is applied to maize axes during germination. Rapamycin, a specific inhibitor of the insulin-stimulated signal transduction pathway, prevented S6 rp phosphorylation in maize axes. Moreover, ZmIGF stimulated [35S]methionine incorporation into rps, above the level of overall cytoplasmic proteins. Either incubation with anti-insulin antibody, heat treatment (60°C) or trypsin digestion abolished this ZmIGF effect. It is proposed that ZmIGF is an endogenous maize growth factor that regulates the synthesis of specific proteins through a pathway similar to that of insulin or IGFs in animal tissues.

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Section: Discussionmentioning

confidence: 99%

A maize insulin-like growth factor signals to a transduction pathway that regulates protein synthesis in maize

Flores

Aguilar

Cruz

et al. 2001

Biochemical Journal

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“…The human IGF-II gene has four independent promoters, which are differentially regulated in a tissue-and developmental stage-specific manner (50,51). To determine which IGF-II promoter(s) are activated by EGR1 in LAPC4 prostate cells, we used promoter-specific primers (26) to analyze transcription from the four promoters following EGR1 expression.…”

Section: Table III Validation Of Egr1 Target Genesmentioning

confidence: 99%

EGR1 Target Genes in Prostate Carcinoma Cells Identified by Microarray Analysis

Svaren¹,

Ehrig²,

Abdulkadir³

et al. 2000

Journal of Biological Chemistry

166

133

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The EGR1 transactivator is overexpressed in prostate cancer, and its expression pattern suggests that EGR1 could potentially regulate a number of steps involved in initiation and progression of prostate cancer, such as mitogenesis, invasiveness, angiogenesis, and metastasis. To identify potential EGR1 target genes in an unbiased manner, we have utilized adenovirus-mediated expression of EGR1 in a prostate cancer cell line to identify specific genes that are induced by EGR1. Using oligonucleotide arrays, a number of EGR1-regulated genes were identified and their regulation was confirmed by quantitative reverse transcription-polymerase chain reaction analysis. One of the largest gene classes identified in this screen includes several neuroendocrine-associated genes (neuron-specific enolase, neurogranin), suggesting that EGR1 overexpression may contribute to the neuroendocrine differentiation that often accompanies prostate cancer progression. This screen also identified several growth factors such as insulin-like growth factor-II, platelet-derived growth factor-A, and transforming growth factor-␤1, which have previously been implicated in enhancing tumor progression. The insulin-like growth factor-II gene lies within the 11p15.5 chromosomal locus, which contains a number of other imprinted genes, and EGR1 expression was found to induce at least two other genes in this locus (IPL, p57 KIP2 ). Based on our results, coupling adenoviral overexpression with microarray and quantitative reverse transcription-polymerase chain reaction analyses could be a versatile strategy for identifying target genes of transactivators.

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“…The middle and proximal segments of the P3 promoter together (Ϫ515 to ϩ140) may therefore represent the core promoter. As stated above, several cis elements have already been identified in the proximal segment of the IGF-2 P3 promoter (32). It is likely that some of these factors, such as Sp1 and Egr, also play an important role in the unregulated transcriptional activity of the IGF-2 gene in CaCo2 cells.…”

Section: Discussionmentioning

confidence: 89%

“…Several functional regulatory elements are present in the proximal segment (Ϫ238/ϩ140) of the human IGF-2 P3 promoter (32). P3 contains a TATA-box and a CAAT-box sequence, and both are bound by their cognate factors.…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, several Sp1 sites are present in the proximal promoter, which is very GC-rich. Other zinc finger transcription factors such as the early growth response proteins Egr-1 and Egr-2 can also bind to multiple sites in the proximal promoter, thereby activating transcription (20,32). Interestingly, the Wilms' tumor WT-1 gene product, a tumor suppressor protein, also recognizes the Egr binding sites in the proximal promoter and suppresses the transcriptional activity of the IGF-2 P3 promoter by binding to Egr-l/WT-1 consensus sequences (33).…”

Section: Discussionmentioning

confidence: 99%

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Identification of a Novel Cis Element Required for Cell Density-dependent Down-regulation of Insulin-like Growth Factor-2 P3 Promoter Activity in CaCo2 Cells

Dai

Holthuizen

et al. 2001

Journal of Biological Chemistry

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The activity of the exogenous, full-length insulin-like growth factor-2 (IGF-2) P3 promoter is significantly upregulated during the logarithmic growth phase but rapidly declines in confluent CaCo2 cells undergoing differentiation. Nuclear run-on assays confirmed cell densitydependent regulation of endogenous P3 promoter. To identify regulatory elements in the P3 promoter that may be required for regulating cell density-dependent transcriptional activity, we used the methods of promoter truncation, electrophoretic mobility shift assay, DNase footprinting, and mutation analysis. The relative activity of the full-length (؊1229/؉140) and truncated (؊1090/؉140) promoter was identical, being ϳ19, 27, 7, and 3% of pSV-luc activity on days 3, 5, 7, and 9 of cell culture, respectively. However, truncation to ؊1048 resulted in complete loss of cell density-dependent downregulation of P3 promoter activity on days 7 and 9, suggesting the presence of regulatory elements between ؊1091 and ؊1048 sequence. Further stepwise truncation to ؊515 did not change promoter activity. Truncation to ؊138/؉140 resulted in complete loss of promoter activity, suggesting that the core promoter was within the ؊515/؊138 segment. A 14-base pair footprint (؊1084/ ؊1070) was identified by DNase footprinting within the distal ؊1091/؊1048 segment. Electrophoretic mobility shift assay with wild type and mutant probes confirmed the presence of a novel 7-base pair (CGAGGGC) (؊1084/ ؊1078) cis element (P3-D); its mutation abolished binding. Functionality of P3-D cis element was confirmed by measuring the activity of core P3 promoter ligated to distal P3 segment containing either the mutant or wild type P3-D element. We have, therefore, identified a novel cis element, P3-D, that appears to play a critical role in regulating IGF-2 P3 promoter activity in a cell density/differentiation-dependent manner.

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Regulation of IGF Gene Expression

Cited by 6 publications

References 137 publications

A maize insulin-like growth factor signals to a transduction pathway that regulates protein synthesis in maize

A maize insulin-like growth factor signals to a transduction pathway that regulates protein synthesis in maize

EGR1 Target Genes in Prostate Carcinoma Cells Identified by Microarray Analysis

Identification of a Novel Cis Element Required for Cell Density-dependent Down-regulation of Insulin-like Growth Factor-2 P3 Promoter Activity in CaCo2 Cells

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