Eukaryotic initiation factor 5A is a cellular target of the human immunodeficiency virus type 1 Rev activation domain mediating trans-activation.

Rühl, Michael; Himmelspach, Michèle; Bahr, George M.; Hammerschmid, Franz; Jaksche, Herbert; Wolff, Barbara; Aschauer, Harald; Farrington, G K; Probst, Hans; Bevec, Dorian

doi:10.1083/jcb.123.6.1309

Cited by 265 publications

(233 citation statements)

References 78 publications

(120 reference statements)

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“…In line with this idea is the observation that certain metal chelator inhibitors of deoxyhypusine hydroxylase, the enzyme that catalyzes the final step of hypusine synthesis, cause arrest of mammalian cells at the G 1 /S boundary of the cell cycle (16). Recently, eIF-5A was reported to be a cellular cofactor essential for Rev function in human immunodeficiency virus type 1 replication (41) or Rex function in human T-cell lymphotrophic virus replication (42), thus promoting speculation on its role in the recognition and nuclear export of specific mRNAs. The fact that yeast cells deprived of polyamines and those depleted of eIF-5A or of deoxyhypusine synthase display a similar enlargement suggests the intriguing possibility that eIF-5A may play a role in cell division cycle control.…”

Section: Fig 4 Comparison Of Expression Of Yeast Recombinant Deoxyhmentioning

confidence: 64%

Deoxyhypusine Synthase Activity Is Essential for Cell Viability in the Yeast Saccharomyces cerevisiae

Park

Joe²,

Kang³

1998

Journal of Biological Chemistry

117

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Section: Fig 4 Comparison Of Expression Of Yeast Recombinant Deoxyhmentioning

confidence: 64%

Deoxyhypusine Synthase Activity Is Essential for Cell Viability in the Yeast Saccharomyces cerevisiae

Park

Joe²,

Kang³

1998

Journal of Biological Chemistry

117

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“…Additional effects of Rev are likely to occur at the level of facilitating viral RNA transport or translation. These transport effects could involve the specific interplay of other cellular factors, such as the nucleoporin-like Rab͞Rip proteins (49)(50)(51) or eIF 5A (52,53), with the leucine-rich activation domain of Rev (7), which functions as a nuclear export signal (54,55). Mutation of this leucine-rich domain results in the formation of potent dominant-negative inhibitors of Rev (56), which already have shown promise in early clinical trials (57).…”

Section: Discussionmentioning

confidence: 99%

HIV Rev-dependent binding of SF2/ASF to the Rev response element: Possible role in Rev-mediated inhibition of HIV RNA splicing

Powell

Amaral

et al. 1997

Proc. Natl. Acad. Sci. U.S.A.

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Production of the structural and enzymatic proteins of type 1 human immunodeficiency virus (HIV-1) is controlled by the rev regulatory gene product. The 116-amino acid Rev protein acts by binding to the Rev response element (RRE), a complex RNA stem-loop structure located within the env gene of HIV. Rev exerts a series of posttranscriptional effects, including the inhibition of viral RNA splicing, the activation of nuclear export of incompletely spliced viral RNAs, and the enhancement of translation of RRE-containing RNAs. Our studies now demonstrate that at least one member of the SR family of splicing factors, SF2͞ASF, specifically binds to a subregion of the RRE in vitro in a Rev-dependent manner. Furthermore, expression of high levels of SF2͞ASF inhibits Rev function and impairs HIV replication in vivo. Both the in vitro binding of SF2͞ASF to the Rev͞RRE complex and the in vivo inhibition of Rev action by SF2͞ASF are abrogated by mutation of the N-terminal RNA recognition motif but are not affected by mutation of the C-terminal arginine-serinerich domain. These findings suggest that Rev inhibition of HIV splicing likely involves recruitment of the essential splicing factor SF2͞ASF to the Rev͞RRE complex. However, these inhibitory effects of Rev on viral RNA splicing are apparently overcome by augmenting the intracellular levels of SF2͞ASF expression.Rev is an essential regulatory protein of the type 1 human immunodeficiency virus (HIV-1) that controls production of proteins required for the assembly of infectious virions (1-5). The 9-kb full-length genomic transcript of HIV undergoes a complex series of posttranscriptional splicing events resulting in the generation of more than 20 mRNAs that encode 9 different viral proteins (for review see refs. 6-8). The resultant mRNAs can be grouped in three size classes: the 2-kb viral RNAs are fully spliced and encode the regulatory proteins of HIV, including Rev, Tat, and Nef, whereas the 9-and 4-kb mRNAs encode the structural, enzymatic, and ancillary viral proteins, including Gag, Pol, Vif, Vpu, Vpr, and Env. The appearance of the 4-and 9-kb classes of mRNAs in the cytoplasm is regulated by the Rev protein (1-5). Rev binds specifically to the Rev response element (RRE), a complex 220-nucleotide RNA stem-loop structure located in the env coding sequence. This binding leads to effective cytoplasmic expression of the singly spliced (4 kb) and unspliced (9 kb) viral mRNAs, thus allowing the transition from early-stage regulatory protein synthesis to late-stage structural and enzymatic viral protein production (2, 6, 7). In the absence of Rev, these incompletely spliced RRE-containing transcripts are retained in the nucleus where they are either completely spliced or degraded (6, 7). Various mechanisms have been suggested to explain the action of Rev, including inhibition of viral mRNA splicing, activation of viral RNA transport from the nucleus to the cytoplasm, and enhanced translation of RRE-containing viral RNAs (1, 6-8). These mechanisms are not mutually ex...

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“…This localization is consistent with a putative role for eIF6 in the coordination of nuclear and cytoplasmic events. A nuclear localization has been reported for two other eIFs, namely, eIF5A (25) and eIF-4E (26).…”

Section: Discussionmentioning

confidence: 99%

“…For example, eIF5A is believed to mediate the nucleo-cytoplasmic transport of specific cellular RNAs and ribonucleoproteins through the nuclear pores (25,41,42). It will therefore be of interest to identify proteins that interact with eIF6 to clarify the role(s) of this essential protein.…”

Section: Discussionmentioning

confidence: 99%

Cloning of Murine Translation Initiation Factor 6 and Functional Analysis of the Homologous Sequence YPR016c in Saccharomyces cerevisiae

Wood¹,

Ashby²,

Grünfeld³

et al. 1999

Journal of Biological Chemistry

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The cDNA sequence of a murine gene whose expression was up-regulated after epidermal injury was cloned utilizing differential display. The full-length cDNA was isolated by 3 and 5 rapid amplification of cDNA ends from mouse liver. The predicted protein is >97% identical to the human sequence for eukaryotic translation initiation factor (eIF) 6, thus identifying the gene as murine eIF6. Functional studies of the yeast eIF6 homolog, YPR016c, were initiated in Saccharomyces cerevisiae to determine the cellular role(s) of eIF6. Complete deletion of the YPR016c coding sequence was lethal. Viability was restored in the presence of either YPR016c or murine eIF6, when either was expressed as aminoterminal green fluorescent protein fusion protein. Moreover, both fusion proteins localized to nuclear/perinuclear compartments in their respective yeast strains. When the expression of YPR016c-green fluorescent protein was repressed, there was a dramatic reduction in the 60 S ribosomal subunit and polysome content and decreased 80S monosome content. Additionally, the YPR016c-depleted cells arrested in G 1 . These studies show that YPR016c, which encodes yeast eIF6, is necessary for maximal polysome formation and plays an important role in determining free 60 S ribosomal subunit content.The epidermal permeability barrier is composed of intercellular lipids in the stratum corneum and protects skin from dessication. After acute permeability barrier disruption, induced experimentally by either tape stripping or topical acetone treatment, the barrier is restored by a coordinate process involving increased lipid synthesis (1, 2), cytokine and growth factor production (3-5), and DNA replication (6, 7). Whereas many of these repair responses are linked directly to an increase in transepidermal water loss (a measure of barrier integrity), others, such as increased pro-inflammatory cytokine production, may be the result of the attendant epidermal cell injury that accompanies barrier disruption (3,8). Utilizing differential display, we have identified a protein whose mRNA was up-regulated after acute permeability barrier disruption. The corresponding cDNA was cloned and sequenced. Here we report that based on its high degree of predicted amino acid sequence identity (Ͼ97%), the cDNA is the murine ortholog of the recently cloned human translation initiation factor 6 (eIF6) 1 for which a yeast homolog has been identified (9). The role of eIF6 in translation is not firmly established (10). 80 S ribosomal subunits, which are released from polysomes after translation termination, are in equilibrium with 40 S and 60 S subunits. Purified eIF6 from rabbit reticulocyte lysates binds to the 60 S ribosomal subunit and exhibits ribosome anti-association activity in an in vitro assay (11). eIF6 and another translation initiation factor, eIF3 (a multiprotein complex that also exhibits anti-association activity via its interaction with the 40 S ribosomal subunit), are thought to regulate the supply of ribosomal subunits necessary for translation initia...

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Eukaryotic initiation factor 5A is a cellular target of the human immunodeficiency virus type 1 Rev activation domain mediating trans-activation.

Cited by 265 publications

References 78 publications

Deoxyhypusine Synthase Activity Is Essential for Cell Viability in the Yeast Saccharomyces cerevisiae

Deoxyhypusine Synthase Activity Is Essential for Cell Viability in the Yeast Saccharomyces cerevisiae

HIV Rev-dependent binding of SF2/ASF to the Rev response element: Possible role in Rev-mediated inhibition of HIV RNA splicing

Cloning of Murine Translation Initiation Factor 6 and Functional Analysis of the Homologous Sequence YPR016c in Saccharomyces cerevisiae

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