Differential polysomal localization of human insulin‐like‐growth‐factor‐2 mRNAs in cell lines and foetal liver

Moor, Cornelia H. de; Jansen, M.; Sussenbach, J.S.; Brande, J. L. Van den

doi:10.1111/j.1432-1033.1994.tb18953.x

Cited by 27 publications

(20 citation statements)

References 36 publications

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“…Leader 2 is relatively long (411 nt), and its mRNA is translated efficiently, particularly in fetal liver [17,18]. In agreement with these data, we found that chimaeric leader 2-luciferase mRNA was efficiently translated, particularly in RD cells that express high levels of endogenous IGF-II mRNA [19].…”

Section: Discussionsupporting

confidence: 73%

Human insulin-like growth factor II leader 2 mediates internal initiation of translation

Pedersen

Christiansen

Larsen³

et al. 2002

Biochemical Journal

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Insulin-like growth factor II (IGF-II) is a fetal growth factor, which belongs to the family of insulin-like peptides. During fetal life, the IGF-II gene generates three mRNAs with different 5′ untranslated regions (UTRs), but identical coding regions and 3′ UTRs. We have shown previously that IGF-II leader 3 mRNA translation is regulated by a rapamycin-sensitive pathway, whereas leader 4 mRNA is constitutively translated, but so far the significance of leader 2 mRNA has been unclear. Here, we show that leader 2 mRNA is translated efficiently in an eIF4E-independent manner. In a bicistronic vector system, the 411 nt leader 2 was capable of internal initiation via a phylogenetically conserved internal ribosome entry site (IRES), located in the 3′ half of the leader. The IRES is composed of an approx. 120 nt ribosome recruitment element, followed by an 80 nt spacer region, which is scanned by the ribosomal pre-initiation complex. Since cap-dependent translation is down-regulated during cell division, leader 2 might facilitate a continuous IGF-II production in rapidly dividing cells during development.

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Section: Discussionsupporting

confidence: 73%

Human insulin-like growth factor II leader 2 mediates internal initiation of translation

Pedersen

Christiansen

Larsen³

et al. 2002

Biochemical Journal

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“…Thus, a GH-induced doubling of the mRNA level, as shown in vivo, may in fact be of physiological significance. It has previously been shown that the different IGF2 transcripts are subject to differential translational efficiencies, and that the rate of cell proliferation can switch, at least the P3 promoter derived transcript (which is not detected in adult liver), from a non-translatable to a translatable protein complex (Moor et al 1994. It is possible that one of the biological effects of GH is to induce a similar switch to P2-derived transcripts in addition to activation of the promoter.…”

Section: Discussionmentioning

confidence: 99%

“…The efficiency of translation is different for the multiple transcripts, and the mRNA from the P4 promoter has been shown to be constitutively translated, whereas the P3 generated transcript is subject to a growthdependent translation, at least in some cell lines and in fetal liver (Moor et al 1994. In addition, the hepatocellular carcinoma cell line, Hep3B, shows a variability in IGF2 transcription in relation to different growth conditions, i.e.…”

Section: Introductionmentioning

confidence: 99%

GH is a regulator of IGF2 promoter-specific transcription in human liver

Horn

Ekström²,

Ellis³

et al. 2002

Journal of Endocrinology

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The regulation of the insulin-like growth factor-II gene (IGF2) is complex and involves the usage of four promoters resulting in different 5 untranslated regions, but with a common translated product. The IGF2 gene product is a mitogenic and survival factor that has been suggested to be important for a normal fetal development and cancer. In this paper we present evidence suggesting that the human IGF2 gene is regulated by GH, and that this regulation occurs in a promoter-specific way. Three lines of evidence support this finding. First, in vivo data from patients treated with GH (one injection or daily injections for 5 consecutive days) showed an increase in the IGF2 P2 promoter derived transcript after acute treatment, and of the P4 promoter transcript after shortterm treatment while the P1 promoter derived transcript did not show any significant change. Secondly, isolated human liver cells treated with GH for 2 h displayed an upregulation of the P2 promoter derived transcript. Thirdly, employing transfection experiments in GHreceptor positive CHO cells with P2 and P4 promoterluciferase constructs, an upregulation by GH was evident, while a P1 promoter construct was unresponsive. We suggest that GH may be a physiological regulator of IGF2 in humans.

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“…The IGF2 mRNAs are translated with dierent eciencies, depending on the promoter and hence on the 5' untranslated region they contain. In general, the transcript initiated at promoter P3 is less eciently translated than the others (de Moor et al, 1994).…”

Section: Introductionmentioning

confidence: 99%

Cloning of breakpoints in and downstream the IGF2 gene that are associated with overexpression of IGF2 transcripts in colorectal tumours

et al. 1999

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The human IGF2 gene belongs to a group of imprinted genes clustered on the short arm of chromosome 11, band p15.5. It contains 9 exons and spans over 30 kb. IGF2 mRNA overexpression has been reported in human tumours and in some inherited growth disorders. It was recently demonstrated that IGF2 mRNA overexpression contributes to tumour progression and that loss of parental imprinting as well as altered transcription factors are contributing to this overexpression. We have reported structural alterations in the 3' region of the IGF2 gene in two colorectal tumours that overexpressed the IGF2 transcript by 200-and 800-fold. We cloned by the vectorette-PCR strategy, genomic DNA fragments containing the breakpoints from these tumours. The sequencing of these fragments positioned the breakpoint 2 kb downstream the IGF2 gene in one tumour, and in exon 9 in the second. Both breakpoints occurred in regions containing repetitive elements: a TGGA repeat we have identi®ed downstream the gene, and the (CA)n repetition in exon 9. We hypothesize that a negative regulatory element, located downstream the IGF2 gene, has been deleted following these structural alterations and leads to IGF2 gene overexpression.

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Differential polysomal localization of human insulin‐like‐growth‐factor‐2 mRNAs in cell lines and foetal liver

Cited by 27 publications

References 36 publications

Human insulin-like growth factor II leader 2 mediates internal initiation of translation

Human insulin-like growth factor II leader 2 mediates internal initiation of translation

GH is a regulator of IGF2 promoter-specific transcription in human liver

Cloning of breakpoints in and downstream the IGF2 gene that are associated with overexpression of IGF2 transcripts in colorectal tumours

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