Disruption of TFIIH activities generates a stress gene expression response and reveals possible new targets against cancer.

Abstract:

:Disruption of the enzymatic activities of the transcription factor TFIIH by the small molecules Triptolide (TPL) or THZ1 could be used against cancer. Here, we used the MCF10A-ErSrc oncogenesis model to compare the effect of TFIIH inhibitors between transformed cells and their progenitors. We report that tumour cells exhibited highly increased sensitivity to TPL or THZ1 and that the combination of both had a synergic effect. TPL affects the interaction between XPB and p52, causing a reduction in the levels of XPB, p52 and p8, but not other TFIIH subunits. RNA-Seq and RNAPII-ChIP-Seq experiments showed that although the levels of many transcripts were reduced, the levels of a significant number were increased after TPL treatment, with maintained or increased RNAPII promoter occupancy. A significant number of these genes encode for factors that have been related to tumour growth and metastasis, suggesting that transformed cells might rapidly develop resistance to TPL/THZ inhibitors. Some of these genes were also overexpressed in response to THZ1, of which depletion enhances the toxicity of TPL, and are possible new targets against cancer.

journal_name

Open Biol

journal_title

Open biology

authors

Uriostegui-Arcos M,Aguayo-Ortiz R,Valencia-Morales MDP,Melchy-Pérez E,Rosenstein Y,Dominguez L,Zurita M

doi

10.1098/rsob.200050

subject

Has Abstract

pub_date

2020-06-01 00:00:00

pages

200050

issue

6

issn

2046-2441

journal_volume

10

pub_type

杂志文章
  • Biosynthesis and biology of mammalian GPI-anchored proteins.

    abstract::At least 150 human proteins are glycosylphosphatidylinositol-anchored proteins (GPI-APs). The protein moiety of GPI-APs lacking transmembrane domains is anchored to the plasma membrane with GPI covalently attached to the C-terminus. The GPI consists of the conserved core glycan, phosphatidylinositol and glycan side ch...

    journal_title:Open biology

    pub_type: 杂志文章

    doi:10.1098/rsob.190290

    authors: Kinoshita T

    更新日期:2020-03-01 00:00:00

  • Heterotrimeric G protein signalling in the plant kingdom.

    abstract::In animals, heterotrimeric G proteins, comprising α-, β-and γ-subunits, perceive extracellular stimuli through cell surface receptors, and transmit signals to ion channels, enzymes and other effector proteins to affect numerous cellular behaviours. In plants, G proteins have structural similarities to the correspondin...

    journal_title:Open biology

    pub_type: 杂志文章,评审

    doi:10.1098/rsob.120186

    authors: Urano D,Chen JG,Botella JR,Jones AM

    更新日期:2013-03-27 00:00:00

  • Sphingolipids: membrane microdomains in brain development, function and neurological diseases.

    abstract::Sphingolipids are highly enriched in the nervous system where they are pivotal constituents of the plasma membranes and are important for proper brain development and functions. Sphingolipids are not merely structural elements, but are also recognized as regulators of cellular events by their ability to form microdoma...

    journal_title:Open biology

    pub_type: 杂志文章,评审

    doi:10.1098/rsob.170069

    authors: Olsen ASB,Færgeman NJ

    更新日期:2017-05-01 00:00:00

  • Correlating efficacy and desensitization with GluK2 ligand-binding domain movements.

    abstract::Gating of AMPA- and kainate-selective ionotropic glutamate receptors can be defined in terms of ligand affinity, efficacy and the rate and extent of desensitization. Crucial insights into all three elements have come from structural studies of the ligand-binding domain (LBD). In particular, binding-cleft closure is as...

    journal_title:Open biology

    pub_type: 杂志文章

    doi:10.1098/rsob.130051

    authors: Nayeem N,Mayans O,Green T

    更新日期:2013-05-29 00:00:00

  • A brain-derived metric for preferred kinetic stimuli.

    abstract::We here address the question of whether there is any correlation between subjective preference for simple configurations within a specific visual domain such as motion and strength of activity in visual areas in which that domain is emphasized. We prepared several distinctive patterns of dots in motion with various ch...

    journal_title:Open biology

    pub_type: 杂志文章

    doi:10.1098/rsob.120001

    authors: Zeki S,Stutters J

    更新日期:2012-02-01 00:00:00

  • The telomeric protein AKTIP interacts with A- and B-type lamins and is involved in regulation of cellular senescence.

    abstract::AKTIP is a shelterin-interacting protein required for replication of telomeric DNA. Here, we show that AKTIP biochemically interacts with A- and B-type lamins and affects lamin A, but not lamin C or B, expression. In interphase cells, AKTIP localizes at the nuclear rim and in discrete regions of the nucleoplasm just l...

    journal_title:Open biology

    pub_type: 杂志文章

    doi:10.1098/rsob.160103

    authors: Burla R,Carcuro M,Torre ML,Fratini F,Crescenzi M,D'Apice MR,Spitalieri P,Raffa GD,Astrologo L,Lattanzi G,Cundari E,Raimondo D,Biroccio A,Gatti M,Saggio I

    更新日期:2016-08-01 00:00:00

  • Non-invasive prenatal diagnosis by massively parallel sequencing of maternal plasma DNA.

    abstract::The presence of foetal DNA in the plasma of pregnant women has opened up new possibilities for non-invasive prenatal diagnosis. The use of circulating foetal DNA for the non-invasive prenatal detection of foetal chromosomal aneuploidies is challenging as foetal DNA represents a minor fraction of maternal plasma DNA. I...

    journal_title:Open biology

    pub_type: 杂志文章

    doi:10.1098/rsob.120086

    authors: Lo YM

    更新日期:2012-06-01 00:00:00

  • Dependency relationships between IFT-dependent flagellum elongation and cell morphogenesis in Leishmania.

    abstract::Flagella have multiple functions that are associated with different axonemal structures. Motile flagella typically have a 9 + 2 arrangement of microtubules, whereas sensory flagella normally have a 9 + 0 arrangement. Leishmania exhibits both of these flagellum forms and differentiation between these two flagellum form...

    journal_title:Open biology

    pub_type: 杂志文章

    doi:10.1098/rsob.180124

    authors: Sunter JD,Moreira-Leite F,Gull K

    更新日期:2018-11-21 00:00:00

  • Wnt signalling induces accumulation of phosphorylated β-catenin in two distinct cytosolic complexes.

    abstract::Wnt/β-catenin signalling controls development and adult tissue homeostasis and causes cancer when inappropriately activated. In unstimulated cells, an Axin1-centred multi-protein complex phosphorylates the transcriptional co-activator β-catenin, marking it for degradation. Wnt signalling antagonizes β-catenin proteoly...

    journal_title:Open biology

    pub_type: 杂志文章

    doi:10.1098/rsob.140120

    authors: Gerlach JP,Emmink BL,Nojima H,Kranenburg O,Maurice MM

    更新日期:2014-11-01 00:00:00

  • Neutrophil heterogeneity in health and disease: a revitalized avenue in inflammation and immunity.

    abstract::Leucocytes form the principal cellular components of immunity and inflammation, existing as multiple subsets defined by distinct phenotypic and functional profiles. To date, this has most notably been documented for lymphocytes and monocytes. In contrast, as neutrophils are traditionally considered, to be short-lived,...

    journal_title:Open biology

    pub_type: 杂志文章,评审

    doi:10.1098/rsob.120134

    authors: Beyrau M,Bodkin JV,Nourshargh S

    更新日期:2012-11-01 00:00:00

  • Atypical centrioles are present in Tribolium sperm.

    abstract::Typical centrioles are made of microtubules organized in ninefold symmetry. Most animal somatic cells have two centrioles for normal cell division and function. These centrioles originate from the zygote, but because the oocyte does not provide any centrioles, it is surprising that the zygotes of many animals are thou...

    journal_title:Open biology

    pub_type: 杂志文章

    doi:10.1098/rsob.160334

    authors: Fishman EL,Jo K,Ha A,Royfman R,Zinn A,Krishnamurthy M,Avidor-Reiss T

    更新日期:2017-03-01 00:00:00

  • TAK1: a potent tumour necrosis factor inhibitor for the treatment of inflammatory diseases.

    abstract::Aberrant tumour necrosis factor (TNF) signalling is a hallmark of many inflammatory diseases including rheumatoid arthritis (RA), irritable bowel disease and lupus. Maladaptive TNF signalling can lead to hyper active downstream nuclear factor (NF)-κβ signalling in turn amplifying a cell's inflammatory response and exa...

    journal_title:Open biology

    pub_type: 杂志文章

    doi:10.1098/rsob.200099

    authors: Totzke J,Scarneo SA,Yang KW,Haystead TAJ

    更新日期:2020-09-01 00:00:00

  • Control of the dynamics and homeostasis of the Drosophila Hedgehog receptor Patched by two C2-WW-HECT-E3 Ubiquitin ligases.

    abstract::The conserved Hedgehog (HH) signals control animal development, adult stem cell maintenance and oncogenesis. In Drosophila, the HH co-receptor Patched (PTC) controls both HH gradient formation and signalling. PTC is post-translationally downregulated by HH, which promotes its endocytosis and destabilization, but the m...

    journal_title:Open biology

    pub_type: 杂志文章

    doi:10.1098/rsob.150112

    authors: Brigui A,Hofmann L,Argüelles C,Sanial M,Holmgren RA,Plessis A

    更新日期:2015-10-01 00:00:00

  • Peripheral self-reactivity regulates antigen-specific CD8 T-cell responses and cell division under physiological conditions.

    abstract::T-cell identity is established by the expression of a clonotypic T-cell receptor (TCR), generated by somatic rearrangement of TCRα and β genes. The properties of the TCR determine both the degree of self-reactivity and the repertoire of antigens that can be recognized. For CD8 T cells, the relationship between TCR ide...

    journal_title:Open biology

    pub_type: 杂志文章

    doi:10.1098/rsob.160293

    authors: Swee LK,Tan ZW,Sanecka A,Yoshida N,Patel H,Grotenbreg G,Frickel EM,Ploegh HL

    更新日期:2016-11-01 00:00:00

  • The Drosophila chromosomal protein Mst77F is processed to generate an essential component of mature sperm chromatin.

    abstract::In most animals, the bulk of sperm DNA is packaged with sperm nuclear basic proteins (SNBPs), a diverse group of highly basic chromosomal proteins notably comprising mammalian protamines. The replacement of histones with SNBPs during spermiogenesis allows sperm DNA to reach an extreme level of compaction, but little i...

    journal_title:Open biology

    pub_type: 杂志文章

    doi:10.1098/rsob.160207

    authors: Kimura S,Loppin B

    更新日期:2016-11-01 00:00:00

  • Core regulatory circuitries in defining cancer cell identity across the malignant spectrum.

    abstract::Gene expression programmes driving cell identity are established by tightly regulated transcription factors that auto- and cross-regulate in a feed-forward manner, forming core regulatory circuitries (CRCs). CRC transcription factors create and engage super-enhancers by recruiting acetylation writers depositing permis...

    journal_title:Open biology

    pub_type: 杂志文章

    doi:10.1098/rsob.200121

    authors: Jahangiri L,Tsaprouni L,Trigg RM,Williams JA,Gkoutos GV,Turner SD,Pereira J

    更新日期:2020-07-01 00:00:00

  • Linear ubiquitin chains: enzymes, mechanisms and biology.

    abstract::Ubiquitination is a versatile post-translational modification that regulates a multitude of cellular processes. Its versatility is based on the ability of ubiquitin to form multiple types of polyubiquitin chains, which are recognized by specific ubiquitin receptors to induce the required cellular response. Linear ubiq...

    journal_title:Open biology

    pub_type: 杂志文章,评审

    doi:10.1098/rsob.170026

    authors: Rittinger K,Ikeda F

    更新日期:2017-04-01 00:00:00

  • An miRNA fingerprint using neural-enriched extracellular vesicles from blood plasma: towards a biomarker for amyotrophic lateral sclerosis/motor neuron disease.

    abstract::Biomarkers for amyotrophic lateral sclerosis/motor neuron disease (ALS/MND) are currently not clinically available for disease diagnosis or analysis of disease progression. If identified, biomarkers could improve patient outcomes by enabling early intervention and assist in the determination of treatment efficacy. We ...

    journal_title:Open biology

    pub_type: 杂志文章

    doi:10.1098/rsob.200116

    authors: Banack SA,Dunlop RA,Cox PA

    更新日期:2020-06-01 00:00:00

  • Long non-coding RNA LINC00467 regulates hepatocellular carcinoma progression by modulating miR-9-5p/PPARA expression.

    abstract::The aim of this study was to analyse the expression pattern and elucidate the mechanistic involvement of long non-coding RNA LINC00467 in hepatocellular carcinoma (HCC). The relative expression of LINC00467 and microRNA (miR)-9-5p was determined by real-time polymerase chain reaction. Cell viability was measured using...

    journal_title:Open biology

    pub_type: 杂志文章

    doi:10.1098/rsob.190074

    authors: Cai K,Li T,Guo L,Guo H,Zhu W,Yan L,Li F

    更新日期:2019-09-27 00:00:00

  • Primate-specific oestrogen-responsive long non-coding RNAs regulate proliferation and viability of human breast cancer cells.

    abstract::Long non-coding RNAs (lncRNAs) are transcripts of a recently discovered class of genes which do not code for proteins. LncRNA genes are approximately as numerous as protein-coding genes in the human genome. However, comparatively little remains known about lncRNA functions. We globally interrogated changes in the lncR...

    journal_title:Open biology

    pub_type: 杂志文章

    doi:10.1098/rsob.150262

    authors: Lin CY,Kleinbrink EL,Dachet F,Cai J,Ju D,Goldstone A,Wood EJ,Liu K,Jia H,Goustin AS,Kosir MA,Thepsuwan P,Lipovich L

    更新日期:2016-12-01 00:00:00

  • Targeting of Helicobacter pylori thymidylate synthase ThyX by non-mitotoxic hydroxy-naphthoquinones.

    abstract::ThyX is an essential thymidylate synthase that is mechanistically and structurally unrelated to the functionally analogous human enzyme, thus providing means for selective inhibition of bacterial growth. To identify novel compounds with anti-bacterial activity against the human pathogenic bacterium Helicobacter pylori...

    journal_title:Open biology

    pub_type: 杂志文章

    doi:10.1098/rsob.150015

    authors: Skouloubris S,Djaout K,Lamarre I,Lambry JC,Anger K,Briffotaux J,Liebl U,de Reuse H,Myllykallio H

    更新日期:2015-06-01 00:00:00

  • A new role for muscle segment homeobox genes in mammalian embryonic diapause.

    abstract::Mammalian embryonic diapause is a phenomenon defined by the temporary arrest in blastocyst growth and metabolic activity within the uterus which synchronously becomes quiescent to blastocyst activation and implantation. This reproductive strategy temporally uncouples conception from parturition until environmental or ...

    journal_title:Open biology

    pub_type: 杂志文章

    doi:10.1098/rsob.130035

    authors: Cha J,Sun X,Bartos A,Fenelon J,Lefèvre P,Daikoku T,Shaw G,Maxson R,Murphy BD,Renfree MB,Dey SK

    更新日期:2013-04-24 00:00:00

  • TNF-α-induced NF-κB activation upregulates microRNA-150-3p and inhibits osteogenesis of mesenchymal stem cells by targeting β-catenin.

    abstract::Although systemic or local inflammation, commonly featured by cytokine activation, is implicated in patients with bone loss, the underlying mechanisms are still elusive. As microRNAs (miR), a class of small non-coding RNAs involved in essential physiological processes, have been found in bone cells, we aimed to invest...

    journal_title:Open biology

    pub_type: 杂志文章

    doi:10.1098/rsob.150258

    authors: Wang N,Zhou Z,Wu T,Liu W,Yin P,Pan C,Yu X

    更新日期:2016-03-01 00:00:00

  • Or47b plays a role in Drosophila males' preference for younger mates.

    abstract::Reproductive behaviour is important for animals to keep their species existing on Earth. A key question is how to generate more and healthier progenies by choosing optimal mates. In Drosophila melanogaster, males use multiple sensory cues, including vision, olfaction and gustation, to achieve reproductive success. The...

    journal_title:Open biology

    pub_type: 杂志文章

    doi:10.1098/rsob.160086

    authors: Zhuang L,Sun Y,Hu M,Wu C,La X,Chen X,Feng Y,Wang X,Hu Y,Xue L

    更新日期:2016-06-01 00:00:00

  • Expression of a hindlimb-determining factor Pitx1 in the forelimb of the lizard Pogona vitticeps during morphogenesis.

    abstract::With over 9000 species, squamates, which include lizards and snakes, are the largest group of reptiles and second-largest order of vertebrates, spanning a vast array of appendicular skeletal morphology. As such, they provide a promising system for examining developmental and molecular processes underlying limb morphol...

    journal_title:Open biology

    pub_type: 杂志文章

    doi:10.1098/rsob.160252

    authors: Melville J,Hunjan S,McLean F,Mantziou G,Boysen K,Parry LJ

    更新日期:2016-10-01 00:00:00

  • Unravelling the distinct contribution of cell shape changes and cell intercalation to tissue morphogenesis: the case of the Drosophila trachea.

    abstract::Intercalation allows cells to exchange positions in a spatially oriented manner in an array of diverse processes, spanning convergent extension in embryonic gastrulation to the formation of tubular organs. However, given the co-occurrence of cell intercalation and changes in cell shape, it is sometimes difficult to as...

    journal_title:Open biology

    pub_type: 杂志文章

    doi:10.1098/rsob.200329

    authors: Casani S,Casanova J,Llimargas M

    更新日期:2020-11-01 00:00:00

  • A comparison of the Caulobacter NA1000 and K31 genomes reveals extensive genome rearrangements and differences in metabolic potential.

    abstract::The genus Caulobacter is found in a variety of habitats and is known for its ability to thrive in low-nutrient conditions. K31 is a novel Caulobacter isolate that has the ability to tolerate copper and chlorophenols, and can grow at 4 ° C with a doubling time of 40 h. K31 contains a 5.5 Mb chromosome that codes for mo...

    journal_title:Open biology

    pub_type: 杂志文章

    doi:10.1098/rsob.140128

    authors: Ash K,Brown T,Watford T,Scott LE,Stephens C,Ely B

    更新日期:2014-10-01 00:00:00

  • Understanding the mammalian TRAP complex function(s).

    abstract::In eukaryotic cells, about one-third of the synthesized proteins are translocated into the endoplasmic reticulum; they are membrane or lumen resident proteins and proteins direct to the Golgi apparatus. The co-translational translocation takes place through the heterotrimeric protein-conducting channel Sec61 which is ...

    journal_title:Open biology

    pub_type: 杂志文章

    doi:10.1098/rsob.190244

    authors: Russo A

    更新日期:2020-05-01 00:00:00

  • Role of angiocrine signals in bone development, homeostasis and disease.

    abstract::Skeletal vasculature plays a central role in the maintenance of microenvironments for osteogenesis and haematopoiesis. In addition to supplying oxygen and nutrients, vasculature provides a number of inductive factors termed as angiocrine signals. Blood vessels drive recruitment of osteoblast precursors and bone format...

    journal_title:Open biology

    pub_type: 杂志文章,评审

    doi:10.1098/rsob.190144

    authors: Sivan U,De Angelis J,Kusumbe AP

    更新日期:2019-10-31 00:00:00

  • A small mitochondrial protein present in myzozoans is essential for malaria transmission.

    abstract::Myzozoans (which include dinoflagellates, chromerids and apicomplexans) display notable divergence from their ciliate sister group, including a reduced mitochondrial genome and divergent metabolic processes. The factors contributing to these divergent processes are still poorly understood and could serve as potential ...

    journal_title:Open biology

    pub_type: 杂志文章

    doi:10.1098/rsob.160034

    authors: Klug D,Mair GR,Frischknecht F,Douglas RG

    更新日期:2016-04-01 00:00:00