NF-YA overexpression protects from glutamine deprivation

Dolfini, Diletta; Minuzzo, Mario; Sertic, Sarah; Mantovani, Roberto

doi:10.1016/j.bbamcr.2019.118571

Cited by 7 publications

(5 citation statements)

References 60 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Novel pathways with many factors involved are generic terms translation, spliceosome/mRNA splicing, UCH proteinases, cellular senescence, sumoylation and apoptosis. Additional pathways, with fewer factors (10 to 15) are expected from previous work: lipid metabolism (cholesterol biosynthesis, steroid biosynthesis, activation of gene expression by SREBP), metabolism of amino acids and polyamines [86,87]. A few terms are associated with single or very few factors: RMTs methylate histone arginines (RFX5 and MTA3), ABC transporter disorder (E2F8), cargo trafficking to the periciliary membrane (PKNOX1), ER to Golgi anterograde transport (NRF1, CREB3L1, MXI1), Lysosome (MITF), tRNA processing (ATF2) and metabolisms of vitamins (CBF2A2T2/RAD51/USF1).…”

Section: Pathway Enrichment Of Co-localizationsmentioning

confidence: 96%

On the NF-Y regulome as in ENCODE (2019)

et al. 2020

Self Cite

View full text Add to dashboard Cite

NF-Y is a trimeric Transcription Factor -TF- which binds with high selectivity to the conserved CCAAT element. Individual ChIP-seq analysis as well as ENCODE have progressively identified locations shared by other TFs. Here, we have analyzed data introduced by ENCODE over the last five years in K562, HeLa-S3 and GM12878, including several chromatin features, as well RNA-seq profiling of HeLa cells after NF-Y inactivation. We double the number of sequence-specific TFs and co-factors reported. We catalogue them in 4 classes based on co-association criteria, infer target genes categorizations, identify positional bias of binding sites and gene expression changes. Larger and novel co-associations emerge, specifically concerning subunits of repressive complexes as well as RNA-binding proteins. On the one hand, these data better define NF-Y association with single members of major classes of TFs, on the other, they suggest that it might have a wider role in the control of mRNA production.

show abstract

Section: Pathway Enrichment Of Co-localizationsmentioning

confidence: 96%

On the NF-Y regulome as in ENCODE (2019)

et al. 2020

Self Cite

View full text Add to dashboard Cite

show abstract

“…The transcription of potri.011G167500, a potential host protein-coding gene encoding amino acid transmembrane transporter (AAP7), was also downregulated under NO 3 − treatment. AAP7 is homologous to Arabidopsis thaliana AT5G23810, in which this gene is reported to be involved in the uptake of amino acids from xylem (Dolfini et al, 2020).…”

Section: Expression Of Circrnas and Functional Analysis Of Decs Host ...mentioning

confidence: 99%

Identification and Functional Prediction of Poplar Root circRNAs Involved in Treatment With Different Forms of Nitrogen

et al. 2022

View full text Add to dashboard Cite

Circular RNAs (circRNAs) are a class of noncoding RNA molecules with ring structures formed by covalent bonds and are commonly present in organisms, playing an important regulatory role in plant growth and development. However, the mechanism of circRNAs in poplar root responses to different forms of nitrogen (N) is still unclear. In this study, high-throughput sequencing was used to identify and predict the function of circRNAs in the roots of poplar exposed to three N forms [1 mM NO3− (T1), 0.5 mM NH4NO3 (T2, control) and 1 mM NH4+ (T3)]. A total of 2,193 circRNAs were identified, and 37, 24 and 45 differentially expressed circRNAs (DECs) were screened in the T1-T2, T3-T2 and T1-T3 comparisons, respectively. In addition, 30 DECs could act as miRNA sponges, and several of them could bind miRNA family members that play key roles in response to different N forms, indicating their important functions in response to N and plant growth and development. Furthermore, we generated a competing endogenous RNA (ceRNA) regulatory network in poplar roots treated with three N forms. DECs could participate in responses to N in poplar roots through the ceRNA regulatory network, which mainly included N metabolism, amino acid metabolism and synthesis, response to NO3− or NH4+ and remobilization of N. Together, these results provide new insights into the potential role of circRNAs in poplar root responses to different N forms.

show abstract

“…Fourth, metabolic rewiring of cancer cells is associated with, and possibly caused by, overexpression of genes at crucial crossroads in the nucleic acid, amino acid, glucose and lipid metabolic pathways, the vast majority of which are under NF-Y control, based on subunits inactivation and genomic location analysis [12]. Explicative of this is our recent dissection of the glutamine biosynthetic pathway: tumor cells that are sensitive to glutamine starvation become more resistant upon NF-YA stable overexpression entailing up-regulation of CCAAT-dependent genes [62]. In summary, in agreement with other active studies in this field, NF-Y may represent an interesting target for anti-cancer therapy.…”

Section: Discussionmentioning

confidence: 99%

Structural Basis of Inhibition of the Pioneer Transcription Factor NF-Y by Suramin

Nardone

Chaves-Sanjuán

Lapi

et al. 2020

Cells

Self Cite

View full text Add to dashboard Cite

NF-Y is a transcription factor (TF) comprising three subunits (NF-YA, NF-YB, NF-YC) that binds with high specificity to the CCAAT sequence, a widespread regulatory element in gene promoters of prosurvival, cell-cycle-promoting, and metabolic genes. Tumor cells undergo “metabolic rewiring” through overexpression of genes involved in such pathways, many of which are under NF-Y control. In addition, NF-YA appears to be overexpressed in many tumor types. Thus, limiting NF-Y activity may represent a desirable anti-cancer strategy, which is an ongoing field of research. With virtual-screening docking simulations on a library of pharmacologically active compounds, we identified suramin as a potential NF-Y inhibitor. We focused on suramin given its high water-solubility that is an important factor for in vitro testing, since NF-Y is sensitive to DMSO. By electrophoretic mobility shift assays (EMSA), isothermal titration calorimetry (ITC), STD NMR, X-ray crystallography, and molecular dynamics (MD) simulations, we showed that suramin binds to the histone fold domains (HFDs) of NF-Y, preventing DNA-binding. Our analyses, provide atomic-level detail on the interaction between suramin and NF-Y and reveal a region of the protein, nearby the suramin-binding site and poorly conserved in other HFD-containing TFs, that may represent a promising starting point for rational design of more specific and potent inhibitors with potential therapeutic applications.

show abstract

NF-YA overexpression protects from glutamine deprivation

Cited by 7 publications

References 60 publications

On the NF-Y regulome as in ENCODE (2019)

On the NF-Y regulome as in ENCODE (2019)

Identification and Functional Prediction of Poplar Root circRNAs Involved in Treatment With Different Forms of Nitrogen

Structural Basis of Inhibition of the Pioneer Transcription Factor NF-Y by Suramin

Contact Info

Product

Resources

About