The eEF1γ Subunit Contacts RNA Polymerase II and Binds Vimentin Promoter Region

Corbi, Nicoletta; Batassa, Enrico Maria; Pisani, Cinzia; Onori, Annalisa; Certo, Maria Grazia Di; Strimpakos, Georgios; Fanciulli, Maurizio; Mattei, Elisabetta; Passananti, Claudio

doi:10.1371/journal.pone.0014481

Cited by 31 publications

(30 citation statements)

References 46 publications

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“…EF1c also interacts with keratin (Kim et al, 2007b). Interactions with nucleic acids are also included in the repertoire of EF1c functions: it specifically binds to the 39-UTR of vimentin mRNA (Al-Maghrebi et al, 2002), and also binds its promoter region, contacting RNA Pol II (Corbi et al, 2010). Interestingly, the latter report also describes mislocalization of mitochondria and vimentin protein upon EF1c depletion, consistent with our findings of a role for the protein in the regulation of microtubulebased transport.…”

Section: Discussionsupporting

confidence: 88%

Protein kinase Darkener of apricot and its substrate EF1γ regulate organelle transport along microtubules

Serpinskaya

Tuphile

Rabinow

et al. 2013

Journal of Cell Science

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Regulation of organelle transport along microtubules is important for proper distribution of membrane organelles and protein complexes in the cytoplasm. RNAi-mediated knockdown in cultured Drosophila S2 cells demonstrates that two microtubule-binding proteins, a unique isoform of Darkener of apricot (DOA) protein kinase, and its substrate, translational elongation factor EF1c, negatively regulate transport of several classes of membrane organelles along microtubules. Inhibition of transport by EF1c requires its phosphorylation by DOA on serine 294. Together, our results indicate a new role for two proteins that have not previously been implicated in regulation of the cytoskeleton. These results further suggest that the biological role of some of the proteins binding to the microtubule track is to regulate cargo transport along these tracks.

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Section: Discussionsupporting

confidence: 88%

Protein kinase Darkener of apricot and its substrate EF1γ regulate organelle transport along microtubules

Serpinskaya

Tuphile

Rabinow

et al. 2013

Journal of Cell Science

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“…The eEF1γ, upregulated in DU145R80, physically interacts with the RNA polymerase II (pol II) core subunit 3 (RPB3), both in isolation and in the context of the holoenzyme. Importantly, eEF1γ has recently been shown to bind vimentin promoter, and depletion of eEF1γ causes the vimentin protein to be incorrectly compartmentalized and to severely compromise cellular shape and mitochondria localization [47]. According to these observations, eEF1γ overexpression might, at least in part, explain the up-regulation of vimentin we have previous observed in DU145R80 [8].…”

Section: Discussionmentioning

confidence: 78%

Proteomic analysis of zoledronic-acid resistant prostate cancer cells unveils novel pathways characterizing an invasive phenotype

et al. 2014

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Proteomic analysis identified differentially expressed proteins between zoledronic acid-resistant and aggressive DU145R80 prostate cancer (PCa) cells and their parental DU145 cells. Ingenuity Pathway Analysis (IPA) showed a strong relationship between the identified proteins within a network associated with cancer and with homogeneous cellular functions prevalently related with regulation of cell organization, movement and consistent with the smaller and reduced cell-cell contact morphology of DU145R80 cells. The identified proteins correlated in publically available human PCa genomic data with increased tumor expression and aggressiveness. DU145R80 exhibit also a clear increase of alpha-v-(αv) integrin, and of urokinase receptor (uPAR), both included within the same network of the identified proteins. Interestingly, the actin-rich structures localized at the cell periphery of DU145R80 cells are rich of Filamin A, one of the identified proteins and uPAR which, in turn, co-localizes with αv-integrin, in podosomes and/or invadopodia. Notably, the invasive feature of DU145R80 may be prevented by blocking anti-αv antibody. Overall, we unveil a signaling network that physically links the interior of the nucleus via the cytoskeleton to the extracellular matrix and that could dictate PCa aggressiveness suggesting novel potential prognostic markers and therapeutic targets for PCa patients.

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“…In addition, CCHCR1 interacts with the RNA polymerase II subunit 3 (RPB3) [63] and controls its localization. RPB3 regulates the expression and compartmentalization of vimentin through the action of eukaryotic translation elongator factor 1 γ (eEF1γ) [64], [65].Therefore,the effect of CCHCR1 on vimentin organisation could be mediated through its interaction partner RPB3. The inhibitory effect of CCHCR1 isoform 3 on tyrosine phophorylation of STAT3 may also arise from cytoskeletal alterations caused by CCHCR1.…”

Section: Discussionmentioning

confidence: 99%

Centrosomal Localization of the Psoriasis Candidate Gene Product, CCHCR1, Supports a Role in Cytoskeletal Organization

et al. 2012

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CCHCR1 (Coiled-Coil α-Helical Rod protein 1), within the major psoriasis susceptibility locus PSORS1, is a plausible candidate gene with the psoriasis associated risk allele CCHCR1*WWCC. Although its expression pattern in psoriatic skin differs from healthy skin and its overexpression influences cell proliferation in transgenic mice, its role as a psoriasis effector gene has remained unsettled. The 5′-region of the gene contains a SNP (rs3130453) that controls a 5′-extended open reading frame and thus the translation of alternative isoforms. We have now compared the function of two CCHCR1 isoforms: the novel longer isoform 1 and the previously studied isoform 3. In samples of Finnish and Swedish families, the allele generating only isoform 3 shows association with psoriasis (P<10−7). Both isoforms localize at the centrosome, a cell organelle playing a role in cell division. In stably transfected cells the isoform 3 affects cell proliferation and with the CCHCR1*WWCC allele, also apoptosis. Furthermore, cells overexpressing CCHCR1 show isoform- and haplotype-specific influences in the cell size and shape and alterations in the organization and expression of the cytoskeletal proteins actin, vimentin, and cytokeratins. The isoform 1 with the non-risk allele induces the expression of keratin 17, a hallmark for psoriasis; the silencing of CCHCR1 reduces its expression in HEK293 cells. CCHCR1 also regulates EGF-induced STAT3 activation in an isoform-specific manner: the tyrosine phosphorylation of STAT3 is disturbed in isoform 3-transfected cells. The centrosomal localization of CCHCR1 provides a connection to the abnormal cell proliferation and offers a link to possible cellular pathways altered in psoriasis.

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The eEF1γ Subunit Contacts RNA Polymerase II and Binds Vimentin Promoter Region

Cited by 31 publications

References 46 publications

Protein kinase Darkener of apricot and its substrate EF1γ regulate organelle transport along microtubules

Protein kinase Darkener of apricot and its substrate EF1γ regulate organelle transport along microtubules

Proteomic analysis of zoledronic-acid resistant prostate cancer cells unveils novel pathways characterizing an invasive phenotype

Centrosomal Localization of the Psoriasis Candidate Gene Product, CCHCR1, Supports a Role in Cytoskeletal Organization

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