Encyclopedia of Signaling Molecules

2018 Edition
| Editors: Sangdun Choi

TIF6 (eIF6)

Reference work entry
DOI: https://doi.org/10.1007/978-3-319-67199-4_615


 aIF6 in Archae;  Tif6p (in yeast)

Historical Background

  1. (a)

    Isolation and initial characterization of eIF6 – Eukaryotic initiation factor 6 (eIF6), a monomeric protein of about 26.5 kDa, was originally isolated from the postribosomal supernatant of both wheat germ (Russel and Spremulli 1979) and mammalian cell extracts (Valenzuela et al. 1982) based on an in vitro assay that measured the ability of the protein to bind specifically to the 60S ribosomal subunit and to prevent the association of the 60S subunit to the 40S ribosomal subunit to form the 80S ribosomes. Because, the assembly of the 80S initiation complex during initiation of protein synthesis requires a cellular pool of free 40S and 60S ribosomal subunits, eIF6 was thought to play a direct role in the provision of free ribosomal subunits required for initiation of protein synthesis. The protein was therefore classified as a eukaryotic translation initiation factor (eIF), although its function in translation was poorly characterized. Notably, it was shown that eIF6-bound 60S ribosomal subunit is incapable of joining the 40S (48S) initiation complex to form the 80S initiation complex (Valenzuela et al. 1982). It should be noted that recent cryo-electron microscopic studies reveal that eIF6 and the 40S ribosomal subunit share a common binding region on the 60S subunit and cannot bind simultaneously. Thus the ribosomal subunit anti-association activity of eIF6 is due to its ability to physically block intersubunit bridge formation (Gartmann et al. 2010).

  2. (b)
    Functional characterization of eIF6 using molecular genetic analysis in yeast: To facilitate further characterization of eIF6, first a human cDNA (Si et al. 1997) and then the single-copy essential Saccharomyces cerevisiae gene (Si and Maitra 1999; Sanvito et al. 1999) encoding functionally active eIF6, each of 245 amino acids (calculated Mr.,26,558 for human eIF6 and 25,550 for yeast eIF6) were cloned and expressed in Escherichia coli. The two proteins are 72% identical. A molecular genetic analysis in yeast was therefore used by investigators to elucidate the cellular function of eIF6 (Si and Maitra 1999; Sanvito et al. 1999). Using a mutant yeast strain having a conditional eIF6 expression system, these investigators showed that depletion of eIF6 from this mutant strain resulted in inhibition of both cell growth and rate of in vivo protein synthesis. Analysis of the polysome profiles of wild-type and eIF6-depleted cells showed that eIF6-depletion caused a marked reduction in the number of polyribosomes compared with that in wild-type cells (Fig. 1a). However, in contrast to cells depleted of an essential initiation factor, where a reduction in the size of polyribosomes is always accompanied by a marked increase in the number of 80S ribosomes and both free 40S and 60S ribosomal subunits, the decrease in polyribosome content in eIF6-depleted cells is accompanied by a decrease (not increase) in the number of both 80S and 60S ribosomes and concomitant accumulation of half-mer polyribosomes (representing stalled 43S initiation complexes at the 5’-UTR and at the AUG codon of mRNAs awaiting association with 60S ribosomal subunits). Direct determination of total 40S and 60S subunit content of eIF6-depleted cells confirmed that there was a selective reduction of total 60S with respect to total 40S ribosomal subunits, causing a stoichiometric imbalance in the 60S/40S subunit ratio (Fig. 1b) resulting in the formation of half-mer polysomes. These results, along with the observation that lysates of yeast cells lacking eIF6 remained active in translation of mRNA in vitro (Si and Maitra 1999), led to the conclusion that eIF6 does not function as a canonical translation initiation factor for global protein synthesis. Additionally, it was shown that the stability of mature 60S ribosomal particles, synthesized in yeast cells in the presence of eIF6, was not significantly affected following removal of eIF6 from these cells (Basu et al. 2001). Rather evidence clearly indicated that in eIF6-depleted cells, the reduction of 60S ribosomal subunits is due to severe inhibition in the biogenesis of 60S ribosomal subunits. To understand how depletion of eIF6 affects 60S ribosome biogenesis, it is necessary to review very briefly the salient features of ribosome biogenesis.
    TIF6 (eIF6), Fig. 1

    (a) Analysis of the polyribosome profile of eIF6-depleted mutant yeast cells. Lysates of wild-type (wt) and eIF6-depleted mutant yeast cells were subjected to 7–47% (wt/vol) sucrose gradient centrifugation and the A254 profile of the gradient fractions was analyzed in a UV-absorbance monitor. The positions of free 40S, 60S, 80S ribosomes, polyribosomes, and half-mer polyribosomes are indicated. Details of the procedures are in the reference, Si and Maitra (1999). (b), eIF6 depletion results in a decrease in 60S ribosomal subunits. Total ribosome isolated from wild-type and eIF6-depleted cells were dissociated into 40S and 60S ribosomal subunits, and sedimented through 15–40% sucrose gradient and ribosome profiles were determined. (The figures in panels (a) and (b) are reproduced with permission from Si and Maitra 1999). Copyright 1999, the American Society of Microbiology. (c) Schematic representation of the organization and processing sites of 35S pre-rRNA. The 35S precursor RNA contains the sequences for 18S, 25S, and 5.8S rRNAs that are separated by transcribed spacer regions that are removed at various processing steps. The major cleavage sites, the endonucleolytic and exonucleolytic processing steps, processing intermediates, and pathways leading to mature rRNAs are indicated. The processing step that is blocked by eIF6 depletion is also shown (Adapted from the reference Basu et al. 2001)


eIF6 is Essential for the Biogenesis of 60S Ribosomal Subunits

Ribosome biogenesis (reviewed in Kressler et al. 2010; Venema and Tollervey 1999) is a highly conserved process from yeast to mammals and occurs primarily in the nucleolus, where four ribosomal rRNAs (25S in yeast or 28S in mammals), 18S, 5.8S, and 5S are formed, modified co-transcriptionally by pseudouridylation and methylation, and processed during their assembly with 78 (in yeast) and 79 (in mammals) ribosomal proteins into mature 40S and 60S ribosomal subunits. In yeast, where the process has been best characterized, the 18S rRNA of the 40S subunit and the 25S (28S in mammals) and 5.8S rRNAs of the 60S subunit are transcribed in the nucleolus from the rDNA transcription unit by RNA polymerase I as a single large precursor RNA known as the 35S pre-RNA in yeast and 45S pre-rRNA in mammals. The fourth rRNA 5S, also a constituent of the 60S subunit, is transcribed independently from 5S DNA by RNA polymerase III. Immediately following the synthesis of the 35S pre-rRNA, many ribosomal proteins (mostly of the 40S subunits) as well as a large number of transacting nonribosomal proteins and small nucleolar RNPs (SnoRNPs) associate with the 35S pre-rRNA to form the 90S ribonucleoprotein (RNP) particle. Association of the transacting nonribosomal proteins as well as snoRNAs with the preribosomal RNP particles are required for accurate pre-RNA processing, pre-rRNA modification, and ribosome assembly. The 35S pre-rRNA present in the 90S RNP then undergoes a sequence of ordered exonucleolytic trimming and endonucleolytic cleavage reactions (see Fig. 1c) giving rise to several intermediate RNP particles of decreasing size in the nucleus and eventually to a mature 40S ribosomal subunit containing 18S rRNA and a mature 60S ribosomal subunit containing 5.8S and 25S rRNAs. As shown in Fig. 1c, the very first endonucleolytic cleavage at the A2 site results in the formation of pre-40S (43S) and pre-60S (66S) particles. Each precursor particle then follows an independent pathway for subsequent biogenesis in the nucleolus and nucleoplasm, nuclear export and final maturation in the cytoplasm. It should be noted that not all transacting assembly proteins associate simultaneously with the 90S or intermediate pre-40S and pre-60S RNP particles. Rather, these proteins associate with preribosomal RNP particles at different steps of the processing reactions. As the biogenesis and maturation of the pre-60S and pre-40S particles proceed first in nucleolus and then in the nucleoplasm, most of the bound transacting proteins (not the ribosomal proteins) are sequentially released along the biogenesis pathway and recycled in the nucleolus for new rounds of biogenesis. The pre-40S and pre-60S particles that emerge from the nuclear pore complex to the cytoplasm contain only a few bound transacting proteins (reviewed in Kressler et al. 2010; Panse and Johnson 2010). These bound proteins are released in sequence from the preribosomal particles in the cytoplasm to form translation-competent mature ribosomal subunits.

eIF6 is one of the essential 60S ribosomal assembly proteins that associates with the pre-60S ribosomal particles in the nucleolus and is required for the subsequent maturation of the 60S ribosomal particles. In eIF6-depleted cells, while the 20S precursor RNA present in the pre-40S particles is processed to 18S rRNA quite efficiently, most of the 27S pre-rRNA present in the pre-60S particles is degraded without forming 25S and 5.8S rRNAs (Basu et al. 2001). Specifically, depletion of eIF6 blocks the processing of the intermediate 27SB pre-rRNA to 7S and 25.5S pre-rRNAs that are the precursors of 5.8S and 25S mature rRNAs, respectively (Basu et al. 2001 and Fig. 1c). Thus, eIF6 is necessary for the formation of 60S ribosomal subunits because it is necessary for the formation of 25S and 5.8S rRNAs, constituents of the 60S ribosomal subunit.

eIF6 (Tif6p) is Phosphorylated In Vitro and In Vivo in Mammalian and Yeast Cells

In earlier studies (Basu et al. 2003; Ray et al. 2008), it was observed that in both mammalian and yeast cells, eIF6 (Tif6p) is phosphorylated at Ser-174 (major site) and Ser-175 (minor site) by the nuclear isoform of CK1 (CK1α or β in mammals and Hrr25p in yeast). In yeast cells, these are the only sites that are phosphorylated in vivo. Mutation of Ser-174 alone to alanine abolishes phosphorylation of yeast eIF6 by >75% while mutation of both Ser-174 and Ser-175 to alanine or depletion of Hrr25 from yeast cells causes total abolition of eIF6 phosphorylation. More importantly, failure to phosphorylate eIF6 in vivo either by depletion of Hrr25p from yeast cells or alanine replacement of Ser-174 and Ser-175 of Tif6p inhibited efficient processing of preribosomal RNA to form the mature 25S and 5.8S rRNAs and thus 60S ribosome biogenesis in yeast (Ray et al. 2008). Conversely, mutation of Ser-174 alone to alanine abolishes yeast cell growth and viability. Taken together, these results suggest that phosphorylation of Tif6p at Ser-174 and Ser-175 plays an important regulatory role in the function of Tif6p. However, the molecular basis of phosphorylation of eIF6 (Tif6p), is not apparent from these studies.

Nuclear Export of eIF6 (Tif6p) Bound to the pre-60S Ribosomal Particles and Its Subsequent Release

Although the nascent pre-60S particles are mostly assembled in the nucleolus and to a lesser extent in the nucleoplasm, they are exported out of the nucleus to the cytoplasm where final maturation of the pre-60S ribosomal particles occurs to form the mature translationally competent 60S ribosomal subunits. Most of the transacting protein factors that associate with the preribosomal particles during their nucleolar assembly are released in the nucleus prior to the export of the pre-60S particles in the cytoplasm. However, a small number of protein factors including eIF6 (Tif6p) remain bound as the pre-60S particles exit the nucleus and enter the cytoplasm. The cytoplasmic ribosomal maturation pathway involves sequential and ordered release of these bound protein factors by the action of specific energy-consuming cytoplasmic ATPases or GTPases, each of which associates with the preribosomal particles to affect the release of a specific bound factor. In addition, some critical ribosomal proteins are also added at this stage to the 60S particles to make functional 60S ribosomes. The released factors are recycled back to the nucleus for another round of pre-60S ribosome assembly and export. In the ordered release of the bound factors, Tif6p and the nuclear export adapter Nmd3 are the last proteins to be released. Following their release, the pre-60S particles become mature 60 ribosomal subunits and competent to participate in translation.

Mechanism of Release of eIF6 (Tif6p) from the pre-60S Particles

In earlier studies it was reported that in mammalian cells, release of eIF6 from the pre-60S particles is triggered by phosphorylation of eIF6 at Ser-235 by protein kinase C (PKC) and RACK1 (receptor for activated kinase C) (Ceci et al. 2003). However, molecular genetic analysis in yeast cells provided compelling evidence that two cytoplasmic proteins – the GTPase elongation factor-like 1 (Efl1p) (Becam et al. 2001; Senger et al. 2001) and Sdo1, the yeast ortholog of highly conserved mammalian Shwachman–Bodian–Diamond Syndrome (SBDS) protein that is mutated in the inherited bone marrow failure and predisposition to leukemia disorder – genetically interact with the pre-60S particles containing bound eIF6 in the cytoplasm, and act cooperatively to facilitate the release of eIF6 from the pre-60S particles (Menne et al. 2007).

In yeast cells, deletion of either EFL1 or SDO1 confers a very slow growth phenotype. It was also observed that while in wild-type yeast cells, eIF6 (Tif6p) localized predominantly to the nucleolus, there was a large accumulation of Tif6p bound to the pre-60S particles in the cytoplasm of efl1Δ and sdo1Δ cells. Importantly, multiple gain of function TIF6 alleles (having a missense mutation in TIF6) that rescued the growth defect of either sdo1Δ or efl1Δ cells also restored both the nuclear export defect and nucleolar localization of Tif6p. Biochemical analysis showed that in contrast to wild-type Tif6p, which binds to 60S ribosomal subunits with a relatively high affinity, mutant eIF6 in the suppressor strains has a much reduced affinity for 60S subunits and can thus bypass the requirement of Sdo1 and Efl1p for eIF6 release (Menne et al. 2007).

Direct biochemical evidence in support of the requirement of SDO1 and EFL1 in the release of eIF6 from the pre-60S particles came from the recent elegant work of Finch et al. (2011) using a reconstituted in vitro system. These investigators isolated stalled pre-60S ribosomal particles containing bound eIF6 from sbds-deleted mouse liver. Incubation of these eIF6-bound pre-60S particles with purified recombinant human SBDS and EFL1 proteins resulted in the release of eIF6 from the pre-60S particles. This reaction requires GTP binding to EFL1 and subsequent energy of hydrolysis of GTP coupled to eIF6 release. EFL1 alone has a low intrinsic GTPase activity which is markedly stimulated by the addition of purified mature mammalian 60S ribosomal subunits (Senger et al. 2001). Addition of SBDS stimulated further 60S-dependent GTP hydrolysis by EFL1 (Finch et al. 2011). However, despite its 60S ribosome-dependent GTPase activity, EFL1 alone in the absence of SBDS is unable to promote the release of eIF6 from the 60S-found. eIF6 complex although GTP hydrolysis still occurs under these conditions. Further mechanistic studies showed that the essential role of SBDS is to tightly couple the activation of EFL1-mediated GTP hydrolysis on the 60S ribosome to eIF6 release. A conserved lysine residue at position 151 of SBDS, which is mutated in SDS disorder, is required for cooperativity with EFL1 and is essential for this coupling process.

Taken together, these observations of Menne et al. (2007) and Finch et al. (2011) provide compelling evidence that the mechanism of eIF6 release from the pre-60S particles in the cytoplasm during the final maturation of 60S ribosomal subunits is highly conserved between yeast and mammals and involves cooperative interaction of SBDS and EFL1 in mediating the GTP hydrolysis-dependent release of eIF6 from the pre-60S particles. In contrast to the report of Ceci et al. (2003), there was no evidence for the requirement of phosphorylation of eIF6 at Ser-235 for its release.

Recycling of eIF6: Opposing Action of Casein Kinase 1 and Calcineurin Phosphatase in Nucleo-Cytoplasmic Shuttling of eIF6

After eIF6 is released from the pre-60 particles, it must be imported back to the nucleus for continued 60S ribosome biogenesis. eIF6 does not appear to have a nuclear localization signal (NLS) or a nuclear export signal (NES). However, as mentioned before, both the yeast and mammalian eIF6 are phosphorylated by the nuclear isoform of CK1 at Ser-174 and Ser-175 and phosphorylation of eIF6 plays an important physiological role in its function in yeast cells. Additionally, examination of the highly conserved amino acid sequence of eIF6 surrounding the CK1 phosphorylation sites at Ser-174 and Ser-175 shows that in all nucleated species examined so far, the protein also possesses a sequence motif LQVP that is known to be a binding motif for the Ca2+-regulated protein phosphatase calcineurin as shown below (reviewed in Biswas et al. 2011).

168 E D Q D E LS S L L Q V P L V182



S. cerevisiae


Drosophila melanogaster


Methanococcus jannaschii

The presence of a biologically important CK1 phosphorylation site and a calcineurin docking motif in nucleated species gave rise to the hypothesis that the nuclear entry and export of eIF6 might be regulated by CK1 phosphorylation and dephosphorylation by calcineurin as was described for NFAT family of transcription factors in vertebrates and a stress-responsive transcription factor, Crz1p, in yeast (reviewed in Biswas et al. (2011)).

In a recent report, Biswas et al. (2011) presented several lines of evidence which suggest that eIF6 shuttles back and forth between the nucleus and the cytoplasm of mammalian cells. This process is dependent on phosphorylation and dephosphorylation of eIF6 at Ser-174 and Ser-175 mediated by CK1 and the Ca2+/calmodulin-dependent protein phosphatase calcineurin, respectively. Using COS7 cells, it was shown that the nuclear export of eIF6, bound to the pre-60S particles, requires phosphorylation of Ser-174 and Ser-175. Failure to phosphorylate at these sites either by mutation of the serine residues to alanine or treatment of cells with a CK1 inhibitor causes a significant fraction (>90%) of eIF6 to be retained in the nucleus. These observations also suggest that it is the phosphorylated form of eIF6 that is exported to the cytoplasm and is presumably released from the pre-60S particles. For nuclear import of eIF6, the protein phosphatase calcineurin, following its activation by Ca2+, associates with eIF6 that is presumed to be in the phosphorylated form, and appears to play an essential role in eIF6 nuclear import as the localization of eIF6 changes from cytosolic to nuclear subsequent to calcineurin activation in vivo. This event is blocked by the immunosuppressive drug cyclosporin A, that is known to be a specific calcineurin inhibitor suggesting that the dephosphorylated form of eIF6 is imported to the nucleus. At present, it is not known whether nuclear import of dephosphorylated eIF6 requires its association with any cofactor (providing the NLS signal) or eIF6 can enter the nucleus by itself due to its low molecular weight. Additionally, nuclear import and export of eIF6 occur even in the presence of a potent protein synthesis inhibitor cycloheximide and is therefore a reflection of dynamics of import and export of preexisting eIF6 molecules rather than de novo new eIF6 synthesis. The release of eIF6 from the pre-60S particles and its recycling to the nucleus are summarized schematically in Fig. 2.
TIF6 (eIF6), Fig. 2

Schematic representation of the functional pathway of eIF6 in 60S ribosome biogenesis. In the nucleolus, eIF6 associates with the pre-60S particles along with >100 transacting protein factors and is essential for pre-60S ribosome assembly and pre-rRNA processing. eIF6 remains associated with the pre-60S particles during pre-60S maturation in the nucleoplasm as well as during the nuclear export of the pre-60S particles. Nuclear export of eIF6 bound to the pre-60S particles requires phosphorylation of eIF6 at Ser-174 and Ser-175 by the nuclear isoform of CK1. In the cytoplasm, during the final maturation process, two cytoplasmic proteins SBDS/Sdo1 and EFL1/Efl1p interact with the pre-60S particles and catalyze the release of eIF6 coupled to GTP hydrolysis by EFL1. The released eIF6 that is presumably in the phosphorylated form then interacts with Ca2+/calmodulin-regulated protein phosphatase calcineurin and the dephosphorylated form of eIF6, either by itself or by interaction with another as yet unidentified protein factor X containing the NLS signal, is imported to the nucleolus to participate in another round of 60S ribosome biogenesis


eIF6, a highly conserved protein from yeast to mammals, binds to the 60S ribosomal subunit and functions as a ribosomal subunit anti-association factor by preventing premature association with the 40S ribosomal subunit. Molecular genetic analysis in yeast has provided compelling evidence that eIF6 is not a canonical translation initiation factor. Rather, it is essential for 60S ribosome biogenesis and assembly. Specifically, eIF6 associates with the pre-60S particles in the nucleolus along with many other transacting protein factors and is essential for 60S ribosome assembly and pre-rRNA processing to form the mature rRNAs, constituents of the 60S ribosomal particle. Association of eIF6 with the pre-60S particles is also required for the export of the assembled pre-60S particles from the nucleus to the cytoplasm where the release of eIF6 occurs. Nuclear export of the pre-60S particles containing bound eIF6 requires phosphorylation of eIF6 at Ser-174 and Ser-175 by the nuclear isoform of CK1. In the cytoplasm, during the final maturation of the pre-60S particles, two cytoplasmic proteins SBDS/Sdo1 and EFL1/Efl1p interact with the pre-60S particles and catalyze the release of eIF6 coupled to hydrolysis of GTP by EFL1. The released eIF6 that is presumably in the phosphorylated form then interacts with Ca2+/calinodulin-dependent protein phosphatase calcineurin and the dephosphorylated form of eIF6 is imported to the nucleus to participate in another round of 60S ribosome assembly and biogenesis. These observations suggest eIF6 plays an important regulatory role in 60S ribosome biogenesis in eukaryotic cells.

Concluding Remarks

Since the original isolation of eIF6 as a ribosomal subunit anti-association factor, it is now clear that this activity of eIF6 is not utilized to generate free 40S and 60S ribosomal subunits required for initiation of protein synthesis. Rather, association of eIF6 with the pre-60S particles in the nucleolus prevents their premature interaction with the pre-40S particles both in the nucleus and cytoplasm. eIF6 is released only when all other bound factors dissociate from the pre-60 particle leading to the formation of mature 60S ribosomal subunit. Secondly, the essential requirement of SBDS (along with the GTPase EFL1) in the release of eIF6 from the pre-60S particles underscores the importance of this protein in 60S ribosome biogenesis. Mutation of the SBDS gene has been shown to be associated in the inherited leukemia predisposition disorder Shwachman–Diamond syndrome (SDS). Some of the disease-causing mutant proteins are unable to catalyze the release of eIF6 from the pre-60S particles causing defects in 60S ribosome maturation and biogenesis. Thus, SDS has been defined as a “ribosomopathy” by Finch et al. (2011). Finally, the requirement of Ca2+-activated calcineurin phosphatase in the nuclear import of eIF6 could provide a means by which changes in intracellular Ca2+ levels could modulate nuclear import of eIF6, and consequently, nucleolar 60S ribosome biogenesis. Clearly, a detailed molecular investigation of these steps is necessary to understand various quality control mechanisms in the pathway of ribosome biogenesis.




  1. Basu U, Si K, Warner JR, Maitra U. The Sacchamomyces cerevisiae TIF6 gene encoding translation initiation factor 6 is required for 60S ribosomal subunit biogenesis. Mol Cell Biol. 2001;21:1453–62.PubMedPubMedCentralCrossRefGoogle Scholar
  2. Basu U, Si K, Deng H, Maitra U. Phosphorylation of mammalian translation initiation factor 6 and its Saccharomyces cerevisiae homologue Tif6p: evidence that phosphorylation of Tif6p regulates its nucleocytoplasmic distribution and is required for yeast cell growth. Mol Cell Biol. 2003;23:6187–99.PubMedPubMedCentralCrossRefGoogle Scholar
  3. Becam AM, Nasr F, Racki WJ, Zagulski M, Herbert CJ. Ria1p (ynl163c), a protein similar to elongation factor 2, is involved in the biogenesis of 60S subunit of the ribosome in Saccharomyces cerevisiae. Mol Gen Genomics. 2001;266:454–62.CrossRefGoogle Scholar
  4. Biswas A, Mukherjee S, Das S, Shields D, Chow CW, Maitra U. Opposing action of casein kinase 1 and calcineurin in nucleo-cytoplasmic shuttling of mammalian translation initiation factor eIF6. J Biol Chem. 2011;286:3129–38.PubMedCrossRefGoogle Scholar
  5. Ceci M, Gaviraghi C, Gorrini C, Sala LA, Offenhauser N, Marchisio PC, Biffo S. Release of eIF6 (p27BBP) from the 60S subunit allows 80S ribosome assembly. Nature. 2003;426:579–84.PubMedCrossRefGoogle Scholar
  6. Finch AJ, Hilcenko C, Basse N, et al. Uncoupling of GTP hydrolysis from eIF6 release on the ribosome causes Shwachman-Diamond Syndrome. Genes Dev. 2011;25:917–29.PubMedPubMedCentralCrossRefGoogle Scholar
  7. Gartmann M, Blau M, Armache J-P, Mielke T, Topf M, Beckmann R. Mechanism of eIF6-mediated inhibition of ribosomal subunit joining. J Biol Chem. 2010;285:14848–51.PubMedPubMedCentralCrossRefGoogle Scholar
  8. Kressler D, Hurt E, Bassler J. Driving ribosome assembly. Biochem Biophys Acta. 2010;1803:673–83.PubMedCrossRefGoogle Scholar
  9. Menne TF, Goyenechea B, Sanchez-Puig N, Wong CC, Tonkin LM, Ancliff PJ, Brost RL, Costanzo M, Boone C, Warren AJ. The Shwachman-Bodian-Diamond syndrome protein mediates translational activation of ribosomes in yeast. Nat Genet. 2007;39:486–95.PubMedCrossRefGoogle Scholar
  10. Miluzio A, Beugnet A, Volta V, Biffo S. Eukaryotic initiation factor 6 mediates a continuum between 60S ribosome biogenesis and translation. EMBO Rep. 2009;10:459–65.PubMedPubMedCentralCrossRefGoogle Scholar
  11. Panse VG, Johnson AW. Maturation of eukaryotic ribosomes: acquisition of functionality. Trends Biochem Sci. 2010;35:260–6.PubMedPubMedCentralCrossRefGoogle Scholar
  12. Ray P, Basu U, Ray A, Majumdar R, Deng H, Maitra U. The Saccharomyces cerevisiae 60S ribosome biogenesis factor Tif6p is regulated by Hrr25p-mediated phosphorylation. J Biol Chem. 2008;283:9681–91.PubMedPubMedCentralCrossRefGoogle Scholar
  13. Russel DW, Spremulli LL. Purification and characterization of a ribosome dissociation factor (eukaryotic initiation factor 6) from wheat germ. J Biol Chem. 1979;254:8796–800.Google Scholar
  14. Sanvito F, Piatti S, Villa A, Bossi M, Lucchini G, Marchisio PC, Biffo S. The beta 4 integrin interactor p27 (BBP/eIF6) is an essential nuclear matrix protein involved in 60S ribosomal subunit assembly. J Cell Biol. 1999;144:823–37.PubMedPubMedCentralCrossRefGoogle Scholar
  15. Senger B, Lafontaine DLJ, Graindorge J-S, Gadal O, Camasses A, Sanni A, Garnier J-M, Breitenbach M, Hurt E, Fasiolo F. The nucle(ol)ar Tif6p and Efl1p are required for a late cytolasmic step of ribosome synthesis. Mol Cell. 2001;8:1363–73.PubMedCrossRefGoogle Scholar
  16. Si K, Maitra U. The Saccharomyces cerevisiae homologue of mammalian translation initiation factor 6 does not function as a translation initiation factor. Mol Cell Biol. 1999;19:1416–26.PubMedPubMedCentralCrossRefGoogle Scholar
  17. Si K, Chaudhuri J, Chevesich J, Maitra U. Molecular cloning and functional expression of a human cDNA encoding translation initiation factor 6. Proc Natl Acad Sci USA. 1997;94:14285–90.PubMedPubMedCentralCrossRefGoogle Scholar
  18. Valenzuela DM, Chaudhuri A, Maitra U. Eukaryotic ribosomal subunit anti-association activity of calf liver is contained in a single polypeptide chain protein of Mr=25,500 (eukaryotic initiation factor 6). J Biol Chem. 1982;257:7712–9.PubMedPubMedCentralGoogle Scholar
  19. Venema J, Tollervey D. Ribosome synthesis in Saccharomyces cerevisiae. Annu Rev Genet. 1999;33:261–311.PubMedCrossRefGoogle Scholar

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© Springer International Publishing AG 2018

Authors and Affiliations

  1. 1.Department of Developmental and Molecular BiologyAlbert Einstein College of Medicine of Yeshiva UniversityBronxUSA