References of "El Hachem, Najla"
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See detailFBXO32 links ubiquitination to epigenetic reprograming of melanoma cells
Habel, Nadia; El Hachem, Najla ULiege; Soysouvanh, Frederic et al

in Cell Death and Differentiation (2021)

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See detailITGBL1 is a new immunomodulator that favors development of melanoma tumors by inhibiting natural killer cells cytotoxicity
cheli, yann; tulic, meri; El Hachem, Najla ULiege et al

in Molecular Cancer (2021)

Resistances to immunotherapies remains a major hurdle towards a cure for melanoma in numerous patients. An increase in the mesenchymal phenotype and a loss of differentiation have been clearly associated ... [more ▼]

Resistances to immunotherapies remains a major hurdle towards a cure for melanoma in numerous patients. An increase in the mesenchymal phenotype and a loss of differentiation have been clearly associated with resistance to targeted therapies. Similar phenotypes have been more recently also linked to resistance to immune checkpoint therapies. We demonstrated here that the loss of MIcrophthalmia associated Transcription Factor (MITF), a pivotal player in melanocyte differentiation, favors the escape of melanoma cells from the immune system. We identified Integrin beta-like protein 1 (ITGBL1), a secreted protein, upregulated in anti-PD1 resistant patients and in MITFlow melanoma cells, as the key immunomodulator. ITGBL1 inhibited immune cell cytotoxicity against melanoma cells by inhibiting NK cells cytotoxicity and counteracting beneficial effects of anti-PD1 treatment, both in vitro and in vivo. Mechanistically, MITF inhibited RUNX2, an activator of ITGBL1 transcription. Interestingly, VitaminD3, an inhibitor of RUNX2, improved melanoma cells to death by immune cells. In conclusion, our data suggest that inhibition of ITGBL1 might improve melanoma response to immunotherapies. [less ▲]

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See detailWobble tRNA modification and hydrophilic amino acid patterns dictate protein fate.
Rapino, Francesca ULiege; ZHOU, ZHAOLI; RONCERO SANCHEZ, Ana Maria et al

in Nature Communications (2021), 12(1), 2170

Regulation of mRNA translation elongation impacts nascent protein synthesis and integrity and plays a critical role in disease establishment. Here, we investigate features linking regulation of codon ... [more ▼]

Regulation of mRNA translation elongation impacts nascent protein synthesis and integrity and plays a critical role in disease establishment. Here, we investigate features linking regulation of codon-dependent translation elongation to protein expression and homeostasis. Using knockdown models of enzymes that catalyze the mcm(5)s(2) wobble uridine tRNA modification (U(34)-enzymes), we show that gene codon content is necessary but not sufficient to predict protein fate. While translation defects upon perturbation of U(34)-enzymes are strictly dependent on codon content, the consequences on protein output are determined by other features. Specific hydrophilic motifs cause protein aggregation and degradation upon codon-dependent translation elongation defects. Accordingly, the combination of codon content and the presence of hydrophilic motifs define the proteome whose maintenance relies on U(34)-tRNA modification. Together, these results uncover the mechanism linking wobble tRNA modification to mRNA translation and aggregation to maintain proteome homeostasis. [less ▲]

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See detailLoss of tRNA-modifying enzyme Elp3 activates a p53-dependent antitumor checkpoint in hematopoiesis.
Rosu, Adeline ULiege; El Hachem, Najla ULiege; Rapino, Francesca ULiege et al

in The Journal of experimental medicine (2021), 218(3),

The hematopoietic system is highly sensitive to perturbations in the translational machinery, of which an emerging level of regulation lies in the epitranscriptomic modification of transfer RNAs (tRNAs ... [more ▼]

The hematopoietic system is highly sensitive to perturbations in the translational machinery, of which an emerging level of regulation lies in the epitranscriptomic modification of transfer RNAs (tRNAs). Here, we interrogate the role of tRNA anticodon modifications in hematopoiesis by using mouse models of conditional inactivation of Elp3, the catalytic subunit of Elongator that modifies wobble uridine in specific tRNAs. Loss of Elp3 causes bone marrow failure by inducing death in committing progenitors and compromises the grafting activity of hematopoietic stem cells. Mechanistically, Elp3 deficiency activates a p53-dependent checkpoint in what resembles a misguided amino acid deprivation response that is accompanied by Atf4 overactivation and increased protein synthesis. While deletion of p53 rescues hematopoiesis, loss of Elp3 prompts the development of p53-mutated leukemia/lymphoma, and inactivation of p53 and Elongator cooperatively promotes tumorigenesis. Specific tRNA-modifying enzymes thus condition differentiation and antitumor fate decisions in hematopoietic stem cells and progenitors. [less ▲]

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See detailmRNA specific translation in resistant melanoma
El Hachem, Najla ULiege; Close, Pierre ULiege

Poster (2019, September)

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See detailPro-tumoral function of HACE1
El Hachem, Najla ULiege; Ballotti, Robert

in Oncoscience (2018)

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See detailE2F1 inhibition mediates cell death of metastatic melanoma
Rouaud, Florian; Hamouda-Tekaya, Nedra; Cerezo, Michaël et al

in Cell Death and Disease (2018)

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See detailUncovering and deciphering the pro-invasive role of HACE1 in melanoma cells.
El Hachem, Najla ULiege; Habel, Nadia; Naiken, Tanesha et al

in Cell Death and Differentiation (2018)

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See detailThe pro-tumoral function of HACE1
El Hachem, Najla ULiege; Ballotti, Robert

in Oncoscience (2018)

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See detailTumorigenic role of HACE1 in Melanoma
El Hachem, Najla ULiege; ballotti, Robert

Conference (2017)

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See detailRôle pro-tumorigénique de HACE1 dans le mélanome.
El Hachem, Najla ULiege

Doctoral thesis (2017)

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See detailRegulation of fibronectin secretion by HACE1
El Hachem, Najla ULiege; Ballotti, Robert

Poster (2016)

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See detailPro-tumorigenic role of HACE1 in Melanoma
El Hachem, Najla ULiege; Ballotti, Robert

Conference (2015)

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See detailPro-tumorigenic role of HACE1 in Melanoma
El Hachem, Najla ULiege; Ballotti, Robert

Poster (2015)

Detailed reference viewed: 17 (0 ULiège)
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See detailRole of HACE1 in Melanoma
El Hachem, Najla ULiege; Ballotti, Robert

Poster (2015)

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See detailRole of HACE1 protein in Melanoma development
El Hachem, Najla ULiege; Ballotti, Robert

Poster (2015)

Detailed reference viewed: 22 (2 ULiège)