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  1. Article ; Online: Breast cancer plasticity is restricted by a LATS1-NCOR1 repressive axis

    Yael Aylon / Noa Furth / Giuseppe Mallel / Gilgi Friedlander / Nishanth Belugali Nataraj / Meng Dong / Ori Hassin / Rawan Zoabi / Benjamin Cohen / Vanessa Drendel / Tomer Meir Salame / Saptaparna Mukherjee / Nofar Harpaz / Randy Johnson / Walter E. Aulitzky / Yosef Yarden / Efrat Shema / Moshe Oren

    Nature Communications, Vol 13, Iss 1, Pp 1-

    2022  Volume 20

    Abstract: LATS1 is reported to regulate the transition of luminal-basal-like cell plasticity in breast cancer. Here the authors report that LATS1 limits the progression of luminal breast cancer by associating with NCOR1 nuclear corepressor to repress ERα- ... ...

    Abstract LATS1 is reported to regulate the transition of luminal-basal-like cell plasticity in breast cancer. Here the authors report that LATS1 limits the progression of luminal breast cancer by associating with NCOR1 nuclear corepressor to repress ERα-downregulated genes in luminal cells.
    Keywords Science ; Q
    Language English
    Publishing date 2022-11-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: TENT4A Non-Canonical Poly(A) Polymerase Regulates DNA-Damage Tolerance via Multiple Pathways That Are Mutated in Endometrial Cancer

    Umakanta Swain / Gilgi Friedlander / Urmila Sehrawat / Avital Sarusi-Portuguez / Ron Rotkopf / Charlotte Ebert / Tamar Paz-Elizur / Rivka Dikstein / Thomas Carell / Nicholas E. Geacintov / Zvi Livneh

    International Journal of Molecular Sciences, Vol 22, Iss 6957, p

    2021  Volume 6957

    Abstract: TENT4A (PAPD7) is a non-canonical poly(A) polymerase, of which little is known. Here, we show that TENT4A regulates multiple biological pathways and focuses on its multilayer regulation of translesion DNA synthesis (TLS), in which error-prone DNA ... ...

    Abstract TENT4A (PAPD7) is a non-canonical poly(A) polymerase, of which little is known. Here, we show that TENT4A regulates multiple biological pathways and focuses on its multilayer regulation of translesion DNA synthesis (TLS), in which error-prone DNA polymerases bypass unrepaired DNA lesions. We show that TENT4A regulates mRNA stability and/or translation of DNA polymerase η and RAD18 E3 ligase, which guides the polymerase to replication stalling sites and monoubiquitinates PCNA, thereby enabling recruitment of error-prone DNA polymerases to damaged DNA sites. Remarkably, in addition to the effect on RAD18 mRNA stability via controlling its poly(A) tail, TENT4A indirectly regulates RAD18 via the tumor suppressor CYLD and via the long non-coding antisense RNA PAXIP1-AS2 , which had no known function. Knocking down the expression of TENT4A or CYLD , or overexpression of PAXIP1-AS2 led each to reduced amounts of the RAD18 protein and DNA polymerase η, leading to reduced TLS, highlighting PAXIP1-AS2 as a new TLS regulator. Bioinformatics analysis revealed that TLS error-prone DNA polymerase genes and their TENT4A -related regulators are frequently mutated in endometrial cancer genomes, suggesting that TLS is dysregulated in this cancer.
    Keywords TLS ; DNA repair ; poly(A) RNA polymerase ; translesion ; lesion bypass ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
    Subject code 612
    Language English
    Publishing date 2021-06-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Correction

    Eyal Akiva / Gilgi Friedlander / Zohar Itzhaki / Hanah Margalit

    PLoS Computational Biology, Vol 8, Iss

    A Dynamic View of Domain-Motif Interactions.

    2012  Volume 1

    Keywords Biology (General) ; QH301-705.5
    Language English
    Publishing date 2012-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: A dynamic view of domain-motif interactions.

    Eyal Akiva / Gilgi Friedlander / Zohar Itzhaki / Hanah Margalit

    PLoS Computational Biology, Vol 8, Iss 1, p e

    2012  Volume 1002341

    Abstract: Many protein-protein interactions are mediated by domain-motif interaction, where a domain in one protein binds a short linear motif in its interacting partner. Such interactions are often involved in key cellular processes, necessitating their tight ... ...

    Abstract Many protein-protein interactions are mediated by domain-motif interaction, where a domain in one protein binds a short linear motif in its interacting partner. Such interactions are often involved in key cellular processes, necessitating their tight regulation. A common strategy of the cell to control protein function and interaction is by post-translational modifications of specific residues, especially phosphorylation. Indeed, there are motifs, such as SH2-binding motifs, in which motif phosphorylation is required for the domain-motif interaction. On the contrary, there are other examples where motif phosphorylation prevents the domain-motif interaction. Here we present a large-scale integrative analysis of experimental human data of domain-motif interactions and phosphorylation events, demonstrating an intriguing coupling between the two. We report such coupling for SH3, PDZ, SH2 and WW domains, where residue phosphorylation within or next to the motif is implied to be associated with switching on or off domain binding. For domains that require motif phosphorylation for binding, such as SH2 domains, we found coupled phosphorylation events other than the ones required for domain binding. Furthermore, we show that phosphorylation might function as a double switch, concurrently enabling interaction of the motif with one domain and disabling interaction with another domain. Evolutionary analysis shows that co-evolution of the motif and the proximal residues capable of phosphorylation predominates over other evolutionary scenarios, in which the motif appeared before the potentially phosphorylated residue, or vice versa. Our findings provide strengthening evidence for coupled interaction-regulation units, defined by a domain-binding motif and a phosphorylated residue.
    Keywords Biology (General) ; QH301-705.5
    Subject code 500
    Language English
    Publishing date 2012-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: Transcriptome analysis highlights nuclear control of chloroplast development in the shoot apex

    Vijay Dalal / Shlomi Dagan / Gilgi Friedlander / Elinor Aviv / Ralph Bock / Dana Charuvi / Ziv Reich / Zach Adam

    Scientific Reports, Vol 8, Iss 1, Pp 1-

    2018  Volume 9

    Abstract: Abstract In dicots, the key developmental process by which immature plastids differentiate into photosynthetically competent chloroplasts commences in the shoot apical meristem (SAM), within the shoot apex. Using laser-capture microdissection and single- ... ...

    Abstract Abstract In dicots, the key developmental process by which immature plastids differentiate into photosynthetically competent chloroplasts commences in the shoot apical meristem (SAM), within the shoot apex. Using laser-capture microdissection and single-cell RNA sequencing methodology, we studied the changes in the transcriptome along the chloroplast developmental pathway in the shoot apex of tomato seedlings. The analysis revealed the presence of transcripts for different chloroplast functions already in the stem cell-containing region of the SAM. Thereafter, an en masse up-regulation of genes encoding for various proteins occurs, including chloroplast ribosomal proteins and proteins involved in photosynthesis, photoprotection and detoxification of reactive oxygen species. The results highlight transcriptional events that operate during chloroplast biogenesis, leading to the rapid establishment of photosynthetic competence.
    Keywords Medicine ; R ; Science ; Q
    Subject code 580
    Language English
    Publishing date 2018-06-01T00:00:00Z
    Publisher Nature Publishing Group
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article ; Online: CD74 is a regulator of hematopoietic stem cell maintenance.

    Shirly Becker-Herman / Milena Rozenberg / Carmit Hillel-Karniel / Naama Gil-Yarom / Mattias P Kramer / Avital Barak / Lital Sever / Keren David / Lihi Radomir / Hadas Lewinsky / Michal Levi / Gilgi Friedlander / Richard Bucala / Amnon Peled / Idit Shachar

    PLoS Biology, Vol 19, Iss 3, p e

    2021  Volume 3001121

    Abstract: Hematopoietic stem and progenitor cells (HSPCs) are a small population of undifferentiated cells that have the capacity for self-renewal and differentiate into all blood cell lineages. These cells are the most useful cells for clinical transplantations ... ...

    Abstract Hematopoietic stem and progenitor cells (HSPCs) are a small population of undifferentiated cells that have the capacity for self-renewal and differentiate into all blood cell lineages. These cells are the most useful cells for clinical transplantations and for regenerative medicine. So far, it has not been possible to expand adult hematopoietic stem cells (HSCs) without losing their self-renewal properties. CD74 is a cell surface receptor for the cytokine macrophage migration inhibitory factor (MIF), and its mRNA is known to be expressed in HSCs. Here, we demonstrate that mice lacking CD74 exhibit an accumulation of HSCs in the bone marrow (BM) due to their increased potential to repopulate and compete for BM niches. Our results suggest that CD74 regulates the maintenance of the HSCs and CD18 expression. Its absence leads to induced survival of these cells and accumulation of quiescent and proliferating cells. Furthermore, in in vitro experiments, blocking of CD74 elevated the numbers of HSPCs. Thus, we suggest that blocking CD74 could lead to improved clinical insight into BM transplant protocols, enabling improved engraftment.
    Keywords Biology (General) ; QH301-705.5
    Subject code 610
    Language English
    Publishing date 2021-03-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  7. Article ; Online: Using Synthetic Mouse Spike-In Transcripts to Evaluate RNA-Seq Analysis Tools.

    Dena Leshkowitz / Ester Feldmesser / Gilgi Friedlander / Ghil Jona / Elena Ainbinder / Yisrael Parmet / Shirley Horn-Saban

    PLoS ONE, Vol 11, Iss 4, p e

    2016  Volume 0153782

    Abstract: One of the key applications of next-generation sequencing (NGS) technologies is RNA-Seq for transcriptome genome-wide analysis. Although multiple studies have evaluated and benchmarked RNA-Seq tools dedicated to gene level analysis, few studies have ... ...

    Abstract One of the key applications of next-generation sequencing (NGS) technologies is RNA-Seq for transcriptome genome-wide analysis. Although multiple studies have evaluated and benchmarked RNA-Seq tools dedicated to gene level analysis, few studies have assessed their effectiveness on the transcript-isoform level. Alternative splicing is a naturally occurring phenomenon in eukaryotes, significantly increasing the biodiversity of proteins that can be encoded by the genome. The aim of this study was to assess and compare the ability of the bioinformatics approaches and tools to assemble, quantify and detect differentially expressed transcripts using RNA-Seq data, in a controlled experiment. To this end, in vitro synthesized mouse spike-in control transcripts were added to the total RNA of differentiating mouse embryonic bodies, and their expression patterns were measured. This novel approach was used to assess the accuracy of the tools, as established by comparing the observed results versus the results expected of the mouse controlled spiked-in transcripts. We found that detection of differential expression at the gene level is adequate, yet on the transcript-isoform level, all tools tested lacked accuracy and precision.
    Keywords Medicine ; R ; Science ; Q
    Subject code 572
    Language English
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  8. Article ; Online: Runx3-mediated transcriptional program in cytotoxic lymphocytes.

    Joseph Lotem / Ditsa Levanon / Varda Negreanu / Dena Leshkowitz / Gilgi Friedlander / Yoram Groner

    PLoS ONE, Vol 8, Iss 11, p e

    2013  Volume 80467

    Abstract: The transcription factor Runx3 is highly expressed in CD8(+) T and NK cytotoxic lymphocytes and is required for their effective activation and proliferation but molecular insights into the transcription program regulated by Runx3 in these cells are still ...

    Abstract The transcription factor Runx3 is highly expressed in CD8(+) T and NK cytotoxic lymphocytes and is required for their effective activation and proliferation but molecular insights into the transcription program regulated by Runx3 in these cells are still missing. Using Runx3-ChIP-seq and transcriptome analysis of wild type vs. Runx3(-/-) primary cells we have now identified Runx3-regulated genes in the two cell types at both resting and IL-2-activated states. Runx3-bound genomic regions in both cell types were distantly located relative to gene transcription start sites and were enriched for RUNX and ETS motifs. Bound genomic regions significantly overlapped T-bet and p300-bound enhancer regions in Runx3-expressing Th1 helper cells. Compared to resting cells, IL-2-activated CD8(+) T and NK cells contain three times more Runx3-regulated genes that are common to both cell types. Functional annotation of shared CD8(+) T and NK Runx3-regulated genes revealed enrichment for immune-associated terms including lymphocyte activation, proliferation, cytotoxicity, migration and cytokine production, highlighting the role of Runx3 in CD8(+) T and NK activated cells.
    Keywords Medicine ; R ; Science ; Q
    Subject code 570
    Language English
    Publishing date 2013-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  9. Article ; Online: The Transcription and Translation Landscapes during Human Cytomegalovirus Infection Reveal Novel Host-Pathogen Interactions.

    Osnat Tirosh / Yifat Cohen / Alina Shitrit / Odem Shani / Vu Thuy Khanh Le-Trilling / Mirko Trilling / Gilgi Friedlander / Marvin Tanenbaum / Noam Stern-Ginossar

    PLoS Pathogens, Vol 11, Iss 11, p e

    2015  Volume 1005288

    Abstract: Viruses are by definition fully dependent on the cellular translation machinery, and develop diverse mechanisms to co-opt this machinery for their own benefit. Unlike many viruses, human cytomegalovirus (HCMV) does suppress the host translation machinery, ...

    Abstract Viruses are by definition fully dependent on the cellular translation machinery, and develop diverse mechanisms to co-opt this machinery for their own benefit. Unlike many viruses, human cytomegalovirus (HCMV) does suppress the host translation machinery, and the extent to which translation machinery contributes to the overall pattern of viral replication and pathogenesis remains elusive. Here, we combine RNA sequencing and ribosomal profiling analyses to systematically address this question. By simultaneously examining the changes in transcription and translation along HCMV infection, we uncover extensive transcriptional control that dominates the response to infection, but also diverse and dynamic translational regulation for subsets of host genes. We were also able to show that, at late time points in infection, translation of viral mRNAs is higher than that of cellular mRNAs. Lastly, integration of our translation measurements with recent measurements of protein abundance enabled comprehensive identification of dozens of host proteins that are targeted for degradation during HCMV infection. Since targeted degradation indicates a strong biological importance, this approach should be applicable for discovering central host functions during viral infection. Our work provides a framework for studying the contribution of transcription, translation and degradation during infection with any virus.
    Keywords Immunologic diseases. Allergy ; RC581-607 ; Biology (General) ; QH301-705.5
    Subject code 570
    Language English
    Publishing date 2015-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  10. Article ; Online: Strategy of transcription regulation in the budding yeast.

    Sagi Levy / Jan Ihmels / Miri Carmi / Adina Weinberger / Gilgi Friedlander / Naama Barkai

    PLoS ONE, Vol 2, Iss 2, p e

    2007  Volume 250

    Abstract: Cells must adjust their gene expression in order to compete in a constantly changing environment. Two alternative strategies could in principle ensure optimal coordination of gene expression with physiological requirements. First, characters of the ... ...

    Abstract Cells must adjust their gene expression in order to compete in a constantly changing environment. Two alternative strategies could in principle ensure optimal coordination of gene expression with physiological requirements. First, characters of the internal physiological state, such as growth rate, metabolite levels, or energy availability, could be feedback to tune gene expression. Second, internal needs could be inferred from the external environment, using evolutionary-tuned signaling pathways. Coordination of ribosomal biogenesis with the requirement for protein synthesis is of particular importance, since cells devote a large fraction of their biosynthetic capacity for ribosomal biogenesis. To define the relative contribution of internal vs. external sensing to the regulation of ribosomal biogenesis gene expression in yeast, we subjected S. cerevisiae cells to conditions which decoupled the actual vs. environmentally-expected growth rate. Gene expression followed the environmental signal according to the expected, but not the actual, growth rate. Simultaneous monitoring of gene expression and growth rate in continuous cultures further confirmed that ribosome biogenesis genes responded rapidly to changes in the environments but were oblivious to longer-term changes in growth rate. Our results suggest that the capacity to anticipate and prepare for environmentally-mediated changes in cell growth presented a major selection force during yeast evolution.
    Keywords Medicine ; R ; Science ; Q
    Subject code 612 ; 570
    Language English
    Publishing date 2007-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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