Translational Induction of VEGF Internal Ribosome Entry Site Elements During the Early Response to Ischemic Stress

Bornes, Stéphanie; Prado-Lourenço, Leonel; Bastide, Amandine; Zanibellato, Catherine; Iacovoni, Jason S.; Lacazette, Éric; Prats, Anne-Catherine; Touriol, Christian; Piégay, Hervé

doi:10.1161/01.res.0000258873.08041.c9

Cited by 66 publications

(62 citation statements)

References 12 publications

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“…Electroporation was performed as described using an ECM 830 electroporator (BTX Division of Genetronics Inc). 19 For determination of CXCL4 or CXCL4L1 expression in the muscle, the electroporated tibialis anterior was excised and protein extracts, obtained after homogenization in a tissue extraction reagent (Invitrogen), were analyzed by Western blotting and densitometry.…”

Section: Electrotransfer Of Plasmids Encoding Cxcl4 or Cxcl4l1 In Thementioning

confidence: 99%

Functional divergence between 2 chemokines is conferred by single amino acid change

Dubrac

Quemener

Lacazette

et al. 2010

Blood

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CXCL4 and CXCL4L1 are 2 closely related CXC chemokines that exhibit potent antiangiogenic activity. Because interactions with glycosaminoglycans play a crucial role in chemokines activity, we determined the binding parameters of CXCL4 and CXCL4L1 for heparin, heparan sulfate, and chondroitin sulfate B. We further demonstrated that the Leu67/His67 substitution is critical for the decrease in glycan binding of CXCL4L1 but also for the increase of its angiostatic activities. Using a set of mutants, we show that glycan affinity and angiostatic properties are not completely related. These data are reinforced using a monoclonal antibody that specifically recognizes structural modifications in CXCL4L1 due to the presence of His67 and that blocks its biologic activity. In vivo, half-life and diffusibility of CXCL4L1 compared with CXCL4 is strongly increased. As opposed to CXCL4L1, CXCL4 is preferentially retained at its site of expression. These findings establish that, despite small differences in the primary structure, CXCL4L1 is highly distinct from CXCL4.

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Section: Electrotransfer Of Plasmids Encoding Cxcl4 or Cxcl4l1 In Thementioning

confidence: 99%

Functional divergence between 2 chemokines is conferred by single amino acid change

Dubrac

Quemener

Lacazette

et al. 2010

Blood

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“…23,24). The IRES of VEGFA is located in the 5′ untranslated region (UTR) from the transcription initiation site, and the IRES sequence is highly conserved among humans, mice, bovines, and rats (25).…”

Section: Introductionmentioning

confidence: 99%

ARF Suppresses Tumor Angiogenesis through Translational Control of VEGFA mRNA

et al. 2010

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“…3D). These findings were surprising since IRES-A and IRES-B have been previously shown to have similar efficiencies in several systems, both in vitro and in vivo (Bornes et al 2007;Bastide et al 2008). It is likely that miR sensitivity could be a useful test in the classification of cellular IRESes but further studies are required before any general conclusions can be drawn.…”

Section: Resultsmentioning

confidence: 97%

“…VEGF translation has been shown to be driven by two independent IRESes in cell lines (Akiri et al 1998;Huez et al 1998;Stein et al 1998) or in transgenic animal models (Bornes et al 2007). We wanted to evaluate the negative effect of miR-16 on the VEGF 39UTR in the context of the VEGF 59UTR.…”

Section: Resultsmentioning

confidence: 99%

The VEGF IRESes are differentially susceptible to translation inhibition by miR-16

Karaa

Iacovoni²,

Bastide³

et al. 2009

RNA

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Experiments with EMCV (Encephalomyocarditis virus) internal ribosome entry sites (IRESes) have shown that microRNAs (miRs) are unable to inhibit IRES driven translation. However, it is accepted that miRs can inhibit translation through multiple mechanisms, only some of which require interaction with the 59 cap structure. In this report, we first validate the targeting of miR-16 to a predicted binding site in the VEGF 39UTR. We developed a series of experiments to ascertain whether or not miR-16 can inhibit translation of transcripts driven by either of the VEGF IRESes. Our results indicate that cellular IRESes can be classified as both sensitive and insensitive to miR control. While VEGF IRES-A activity was not altered by miR-16 targeting to the 39UTR, IRES-B was susceptible to miR-16 inhibition. Taken together with previous results that show that IRES-B selectively translates the CUG initiated VEGF-121 isoform, we can conclude that the existence of two differentially susceptible IRESes in the VEGF 59UTR leads to even more complex regulatory control of VEGF isoform production. This study demonstrates for the first time the inhibition of cellular IRES driven translation by a miR.

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Translational Induction of VEGF Internal Ribosome Entry Site Elements During the Early Response to Ischemic Stress

Cited by 66 publications

References 12 publications

Functional divergence between 2 chemokines is conferred by single amino acid change

Functional divergence between 2 chemokines is conferred by single amino acid change

ARF Suppresses Tumor Angiogenesis through Translational Control of VEGFA mRNA

The VEGF IRESes are differentially susceptible to translation inhibition by miR-16

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