Transcriptional regulation and biological significance of the insulin like growth factor II gene

Engström, Wilhelm; Shokrai, A.; Otte, Kerstin; Granerus, Marika; Gessbo, Åsa; Bierke, P; Madej, A; Sjölund, Marie; Ward, Andrew

doi:10.1111/j.1365-2184.1998.tb01196.x

Cited by 43 publications

(36 citation statements)

References 178 publications

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“…IGF-II is encoded by a single gene, but multiple promoters and alternative splicing yield multiple protein isoforms (Engstrom et al, 1998). The primary translation product is not N-glycosylated, but addition of N-acetylgalactosamine at four sites occurs upon transport to the Golgi complex, followed by addition of sialic acid (Duguay et al, 1998).…”

Section: Discussionmentioning

confidence: 99%

The Chaperone Activity of GRP94 Toward Insulin-like Growth Factor II Is Necessary for the Stress Response to Serum Deprivation

Ostrovsky

Ahmed

Argon

2009

MBoC

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Insulin-like growth factor (IGF)-II is a hormone with mitogenic activity for many cell types and tissues. We demonstrate that its intracellular processing and secretion strictly depend on the endoplasmic reticulum chaperone glucose-regulated protein (GRP) 94. GRP94 interacts physically and transiently with pro-IGF-II intermediates, and its activity is essential for secretion of active IGF-II, thus establishing IGF-II as a client of GRP94. Embryonic stem (ES) cells that lack GRP94 are hypersensitive to stress conditions such as serum deprivation and die by apoptosis because they cannot respond to the stress by producing active IGF-II. This chaperone-client interaction may explain the previously documented antiapoptotic activity of GRP94 in a number of stress responses.

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Section: Discussionmentioning

confidence: 99%

The Chaperone Activity of GRP94 Toward Insulin-like Growth Factor II Is Necessary for the Stress Response to Serum Deprivation

Ostrovsky

Ahmed

Argon

2009

MBoC

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“…The IGF2 gene comprises many alternatively spliced transcripts from different promoters. In the mouse, the expression of the different mouse IGF2 transcripts is dependent on promoter usage, with P0-derived transcripts only expressed in the labyrinthine layer of the mouse placenta, whereas transcripts from P1-P3 are found throughout the developing embryo and placenta [4]. …”

Section: Gene Structurementioning

confidence: 99%

“…There are 4 promoters and 10 exons (fig. 1), giving rise to different transcripts depending on which promoter the transcript stems from [4]. …”

Section: Gene Structurementioning

confidence: 99%

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Insulin-Like Growth Factor 2 in Development and Disease: A Mini-Review

Bergman

Halje²,

Nordin³

et al. 2012

Gerontology

227

169

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Background: Insulin-like growth factor 2 (IGF2) is a protein hormone known to regulate cell proliferation, growth, migration, differentiation and survival. The gene is parentally imprinted in the sense that transcripts are almost exclusively derived from the paternal allele. Loss of imprinting of the IGF2 gene is a recurrent observation in growth disorders that combine overgrowth with a variety of malignant tumours. Moreover, IGF2 has been proposed to play a role in the development of a variety of seemingly unrelated cancers that play an important role in geriatric medicine, e.g. breast cancer, colon cancer and lung cancer. Finally, IGF2 has been implicated in cardiovascular disease, since, for example, IGF2 has been shown to influence the size of atherosclerotic lesions. Objective: To summarize current knowledge about IGF2, its interactions with binding proteins and receptors and connections with key diseases. Methods: The contents of this paper were based on reviews of existing literature within the field. Results: There is a substantial amount of research linking IGF2 to growth disorders, cancer and to a much lesser degree cardiovascular disease. Some of the studies on IGF2 and tumour growth have yielded conflicting results, for instance regarding its effect on apoptosis. Conclusion: Today, our knowledge on how IGF2 is composed and interacts with receptors has come a long way. However, there is comparatively little information on how IGF2 affects tumour growth and cardiovascular diseases such as atherosclerosis. Thus, further research will be needed to elucidate the impact of IGF2 on key diseases.

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“…IGF2 L3 mRNA expression in the mouse is reported to occur only during fetal life (Newell et al 1994;Engströ m et al 1998); its translation correlates temporally with the onset of expression of the IMP1,2,3 mRNAs, whose expression turns on abruptly at embryonic day 11.5 (E11.5) and is largely extinguished at birth (Nielsen et al 1999). This timing coincides closely with the onset of the biologic action of IGF2, inasmuch as IGF2-deficient embryos show no size deficit before E11 (Baker et al 1993) and overexpression of IGF2 has no impact on embryonic size before E13 (Sun et al 1997).…”

mentioning

confidence: 99%

mTOR phosphorylates IMP2 to promote IGF2 mRNA translation by internal ribosomal entry

Dai¹,

Rapley²,

Angel³

et al. 2011

Genes Dev.

166

157

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Variants in the IMP2 (insulin-like growth factor 2 [IGF2] mRNA-binding protein 2) gene are implicated in susceptibility to type 2 diabetes. We describe the ability of mammalian target of rapamycin (mTOR) to regulate the cap-independent translation of IGF2 mRNA through phosphorylation of IMP2, an oncofetal RNA-binding protein. IMP2 is doubly phosphorylated in a rapamycin-inhibitable, amino acid-dependent manner in cells and by mTOR in vitro. Double phosphorylation promotes IMP2 binding to the IGF2 leader 3 mRNA 59 untranslated region, and the translational initiation of this mRNA through eIF-4E-and 59 cap-independent internal ribosomal entry. Unexpectedly, the interaction of IMP2 with mTOR complex 1 occurs through mTOR itself rather than through raptor. Whereas depletion of mTOR strongly inhibits IMP2 phosphorylation in cells, comparable depletion of raptor has no effect; moreover, the ability of mTOR to phosphorylate IMP2 in vitro is unaffected by the elimination of raptor. Dual phosphorylation of IMP2 at the mTOR sites is evident in the mouse embryo, likely coupling nutrient sufficiency to IGF2 expression and fetal growth. Doubly phosphorylated IMP2 is also widely expressed in adult tissues, including islets of Langerhans.

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Transcriptional regulation and biological significance of the insulin like growth factor II gene

Cited by 43 publications

References 178 publications

The Chaperone Activity of GRP94 Toward Insulin-like Growth Factor II Is Necessary for the Stress Response to Serum Deprivation

The Chaperone Activity of GRP94 Toward Insulin-like Growth Factor II Is Necessary for the Stress Response to Serum Deprivation

Insulin-Like Growth Factor 2 in Development and Disease: A Mini-Review

mTOR phosphorylates IMP2 to promote IGF2 mRNA translation by internal ribosomal entry

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