Aiding and abetting cancer: mRNA export and the nuclear pore

Culjkovic-Kraljacic, Biljana; Borden, Katherine L. B.

doi:10.1016/j.tcb.2013.03.004

Cited by 66 publications

(93 citation statements)

References 87 publications

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“…Although most mRNAs use TREX, TREX-2 and NXF1 receptors to transit through NPCs, a subset of mRNAs use CRM1, the major protein-export receptor (reviewed in REFS 106,107). Proteins are actively transported out of the nucleus by a family of conserved nuclear transport receptors that recognize leucine-rich nuclear export signals (NESs), which bind directly to nucleoporins that line the central channel.…”

Section: Contribution Of Trex-2 To Mrna Export Selectivitymentioning

confidence: 99%

“…Functionally related genes that are preferentially transcribed during cell growth, development or cancer, for example, may be regulated post-transcriptionally by specific mRNA-binding proteins that recognize sequence elements that are conserved among the mRNAs 107,114,115 . Many recent findings support this view.…”

Section: Contribution Of Trex-2 To Mrna Export Selectivitymentioning

confidence: 99%

“…Indeed, driver mutations in cancers such as myelo dysplasia and leukaemia have been identified in the genes encoding splicing factor 3B subunit 1, which anchors the U2 snRNP to pre-mRNA, and splicing factor U2AF 65 kDa subunit, a factor that binds to the polypyrimidine tract of introns and promotes recruitment of the U2 snRNP [125][126][127] . Notably, there is accumulating evidence that dysregulation of mRNA export may contribute to the development of cancer 107 . For example, TREX-2 component GANP is upregulated in lymphomas 128 , and expression of TREX components ALY, CIP29 protein and THOC1 is altered in various cancers, including oral, liver, pancreatic, lung, ovarian and colon [129][130][131][132] .…”

Section: Contribution Of Trex-2 To Mrna Export Selectivitymentioning

confidence: 99%

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Control of mammalian gene expression by selective mRNA export

Wickramasinghe

Laskey

2015

Nat Rev Mol Cell Biol

185

169

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Nuclear export of mRNAs is a crucial step in the regulation of gene expression, linking transcription in the nucleus to translation in the cytoplasm. Although important components of the mRNA export machinery are well characterized, such as transcription-export complexes TREX and TREX-2, recent work has shown that, in some instances, mammalian mRNA export can be selective and can regulate crucial biological processes such as DNA repair, gene expression, maintenance of pluripotency, haematopoiesis, proliferation and cell survival. Such findings show that mRNA export is an unexpected, yet potentially important, mechanism for the control of gene expression and of the mammalian transcriptome.

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Section: Contribution Of Trex-2 To Mrna Export Selectivitymentioning

confidence: 99%

Section: Contribution Of Trex-2 To Mrna Export Selectivitymentioning

confidence: 99%

Section: Contribution Of Trex-2 To Mrna Export Selectivitymentioning

confidence: 99%

See 1 more Smart Citation

Control of mammalian gene expression by selective mRNA export

Wickramasinghe

Laskey

2015

Nat Rev Mol Cell Biol

185

169

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“…TAP is responsible for bulk mRNA export [6] [7]. This export pathway is highly coupled to splicing in humans.…”

Section: Nuclear Exportmentioning

confidence: 99%

Gene Regulation through mRNA Expression

Inose¹,

Mukai²,

Ito³

et al. 2015

ABC

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In eukaryotes, gene expression is achieved by four steps: transcription, processing, nuclear export, and translation. Each step requires multiple factors, and frequently two or more pathways are used by a single gene, enabling strictly regulated gene expression. Importantly, eukaryotes, taking advantage of the separated structures of the nucleus and the cytoplasm, have evolved complex and organized mRNA processing mechanisms that permit sophisticated biological activity. The processes are much more complicated than those found in prokaryotes, in which transcription and translation occur linearly in time and place. Here, we review gene expression, focusing on mRNA processing in the nucleus and the gene regulatory systems found at each step. Combination of gene regulation shows the typical phenotype in each cell. Further understanding of the uncertain mechanisms will uncover the gene regulation through mRNA expression.

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“…eIF4E is dysregulated in an estimated 30% of cancers including specific subtypes of AML(14). eIF4E transforms these cells by driving nuclear export and translation of mRNAs which encode proteins involved in proliferation and survival(15). To associate with these transcripts, eIF4E binds the m 7 G cap on their 5′ end.…”

Section: A New Type Of Drug Resistance: Inducible Drug Modificationmentioning

confidence: 99%

When Will Resistance Be Futile?

Borden

2014

Cancer Research

Self Cite

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Cancer cells rapidly evolve a multitude of defense mechanisms to evade the effects of the oncologist’s drug arsenal. Unfortunately, clinical strategies to overcome these lag far behind. This mismatch likely underlies our inability to implement new durable treatment strategies. Here, a new form of multi-drug resistance, inducible drug glucuronidation, is discussed. This form was discovered while developing means to target a specific oncogene, the eukaryotic translation initiation factor 4E (eIF4E), with its inhibitor ribavirin. In two clinical studies, ribavirin treatment led to substantial clinical responses, but all responding patients eventually relapsed. In most cases, this was due to the overexpression of the sonic hedgehog transcription factor Gli1 which elevated the UDP glucuronsyltransferase UGT1A enzymes. UGT1As add glucuronic acid to many drugs. Indeed, these cells are resistant to not only ribavirin, but also Ara-C, and likely other drugs. Inhibition of Gli1 reduced UGT1As, eliminated drug-glucuronides and renewed sensitivity to ribavirin and Ara-C. These studies highlight that cancer cells and their resistant counterparts metabolize drugs differently from each other as well as from normal cells. Likely these inducible modifications go beyond glucuronidation. Understanding the extent of inducible drug modifications and the pathways that drive expression of the corresponding enzymatic machinery will better position us to finally make resistance futile.

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Aiding and abetting cancer: mRNA export and the nuclear pore

Cited by 66 publications

References 87 publications

Control of mammalian gene expression by selective mRNA export

Control of mammalian gene expression by selective mRNA export

Gene Regulation through mRNA Expression

When Will Resistance Be Futile?

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