IRES in distress: translational regulation of the inhibitor of apoptosis proteins XIAP and HIAP2 during cell stress

Lewis, Stephen M.; Holčı́k, Martin

doi:10.1038/sj.cdd.4401602

Cited by 50 publications

(42 citation statements)

References 74 publications

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“…Accordingly, recent studies showed a very tight regulation of the expression of BIRC2/cIAP1, BIRC3/cIAP2 and BIRC4/XIAP during cell stress such as hypoxia, anoxia, serum deprivation and reticular stress. This is due to the presence of an internal ribosome entry site (IRES) element 69,70 (that allows the continued translation of protein under stress conditions) and an upstream open reading frame (μORF) 71 (that prevents translation under normal condition) in the 5'UTR of mRNA. More over, the expression and stability of IAPs are regulated by molecular chaperone such as heatshock proteins.…”

Section: Iaps: Apoptosis Regulatorsmentioning

confidence: 99%

IAPS : More than just inhibitors of apoptosis proteins

Dubrez

Dupoux²,

Cartier³

2008

Cell Cycle

193

170

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Inhibitors of apoptosis proteins (IAPs) are a conserved family of proteins identified in species ranging from virus, yeasts, nematodes, fishes, flies and mammals. The common structural feature is the presence of at least one Baculovirus IAP Repeat (BIR) domain. Hence, IAPs are also known as BIR-containing proteins (BIRCs). Most of them display anti-apoptotic properties when overexpressed. In drosophila, IAPs are sufficient and necessary to promote cell survival through a direct regulation of apoptotic proteases called caspases. In mammals, BIRC4/XIAP, the most studied IAP member can directly inhibit the activity of caspase-3, 7 and 9. However, this activity is not conserved in other IAPs and physiological relevancies of such anti-caspase activities are still discussed. A detailed analysis of IAP-deficient mice or derived cells, deletion experiments performed in drosophila and zebrafish, or research of protein partners have revealed the importance of IAPs in adaptive response to cellular stress, in cell proliferation, differentiation, signaling, motility and in immune response. This review discusses recent data that help understanding of cellular functions of IAPs.

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Section: Iaps: Apoptosis Regulatorsmentioning

confidence: 99%

IAPS : More than just inhibitors of apoptosis proteins

Dubrez

Dupoux²,

Cartier³

2008

Cell Cycle

193

170

View full text Add to dashboard Cite

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“…33,34 IRES-mediated translation is the preferred method of protein synthesis when cap-mediated translation is attenuated under conditions of stress, like hypoxia, 35,36 genotoxic shock and apoptosis, [37][38][39] or in specific physiological conditions such as mitosis. 40 IRES-containing mRNAs encode for oncogenes like jun, 41 and myc, 42,43 tumor suppressors as p53, 44 and p27, 45 or antiapoptotic factors as bcl2 46,47 and Xiap. 46 One word of caution about cellular IRES sequences: not all the described IRES sequences have received a full physiological validation encompassing multiple technologies.…”

mentioning

confidence: 99%

“…40 IRES-containing mRNAs encode for oncogenes like jun, 41 and myc, 42,43 tumor suppressors as p53, 44 and p27, 45 or antiapoptotic factors as bcl2 46,47 and Xiap. 46 One word of caution about cellular IRES sequences: not all the described IRES sequences have received a full physiological validation encompassing multiple technologies. 48 Therefore, when the existence of IRES-dependent translation is suspected, rigorous experimentation is needed.…”

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confidence: 99%

Translation factors and ribosomal proteins control tumor onset and progression: how?

2013

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Gene expression is shaped by translational control. The modalities and the extent by which translation factors modify gene expression have revealed therapeutic scenarios. For instance, eukaryotic initiation factor (eIF)4E activity is controlled by the signaling cascade of growth factors, and drives tumorigenesis by favoring the translation of specific mRNAs. Highly specific drugs target the activity of eIF4E. Indeed, the antitumor action of mTOR complex 1 (mTORc1) blockers like rapamycin relies on their capability to inhibit eIF4E assembly into functional eIF4F complexes. eIF4E biology, from its inception to recent pharmacological targeting, is proof-of-principle that translational control is druggable. The case for eIF4E is not isolated. The translational machinery is involved in the biology of cancer through many other mechanisms. First, untranslated sequences on mRNAs as well as noncoding RNAs regulate the translational efficiency of mRNAs that are central for tumor progression. Second, other initiation factors like eIF6 show a tumorigenic potential by acting downstream of oncogenic pathways. Third, genetic alterations in components of the translational apparatus underlie an entire class of inherited syndromes known as 'ribosomopathies' that are associated with increased cancer risk. Taken together, data suggest that in spite of their evolutionary conservation and ubiquitous nature, variations in the activity and levels of ribosomal proteins and translation factors generate highly specific effects. Beside, as the structures and biochemical activities of several noncoding RNAs and initiation factors are known, these factors may be amenable to rational pharmacological targeting. The future is to design highly specific drugs targeting the translational apparatus.

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“…Although these factors were not determined in our studies, this regulatory mechanism could be a factor associated with PE as there is increased TGF-b and reduced blood to the placenta reported during this disease. In turn, these factors could be affecting the IRES regulation of XIAP during PE Holcik et al 2003;Holcik and Sonenberg 2005;Lewis and Holcik 2005;Liwak et al 2012;Madazli et al 2003;Van Themsche et al 2010]. The increased nuclear pXIAP present in the placenta could be a trophoblast survival factor important during pregnancy.…”

Section: Discussionmentioning

confidence: 99%

XIAP protein is induced by placenta growth factor (PLGF) and decreased during preeclampsia in trophoblast cells

Arroyo

Price

Chavez

et al. 2014

Systems Biology in Reproductive Medicine

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(2014) XIAP protein is induced by placenta growth factor (PLGF) and decreased during preeclampsia in trophoblast cells, Systems Biology in Reproductive Medicine, 60:5, 263-273, DOI: 10.3109/19396368.2014.927540 To link to this article: https://doi.org/10. 3109/19396368.2014 AbstractIncreased trophoblast apoptosis has been implicated in pregnancies complicated by fetal growth restriction and preeclampsia (EC). We investigated placenta growth factor (PLGF) signaling during trophoblast apoptosis in culture and X-linked inhibitor of apoptosis protein (XIAP) and apoptosis inducible factor (AIF) in the preeclamptic placenta at term was determined. Primary trophoblasts were isolated and serum starved to induce apoptosis. Placenta growth factor was added and apoptosis markers were determined. Term preeclamptic placentae were homogenized and the levels of XIAP and XAF1 protein were assessed. In the absence of serum, primary cultures of term trophoblast showed a 5-fold increase in apoptosis as determined by annexin V binding. The increase in apoptosis induced by serum deprivation was caspase-independent and could be significantly reduced (p50.02) with the addition of 10 ng/ml rh PLGF to the media. In addition, PLGF mediated increased protein expression of the anti-apoptotic XIAP as well as decreased expression of the pro-apoptotic AIF in the primary trophoblast. In preeclamptic placenta, we determined the concomitant decrease in XIAP RNA as well as decreased expression of the phosphorylated XIAP protein. These results were coupled with increased levels of the pro-apoptotic protein XAF1. Our results suggest that PLGF protects trophoblast from caspase independent apoptosis in culture by increasing XIAP production and deceasing AIF. Also, our data suggests that decreased activation of XIAP and increased XAF1 could be factors associated with the increased placental apoptosis observed in the preeclamptic placenta at term.

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IRES in distress: translational regulation of the inhibitor of apoptosis proteins XIAP and HIAP2 during cell stress

Cited by 50 publications

References 74 publications

IAPS : More than just inhibitors of apoptosis proteins

IAPS : More than just inhibitors of apoptosis proteins

Translation factors and ribosomal proteins control tumor onset and progression: how?

XIAP protein is induced by placenta growth factor (PLGF) and decreased during preeclampsia in trophoblast cells

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