Stressing on the nucleolus in cardiovascular disease

Hariharan, Nirmala; Sussman, Mark A.

doi:10.1016/j.bbadis.2013.09.016

Cited by 38 publications

(31 citation statements)

References 64 publications

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“…It is an organization of multiple-component complexes of nucleic acid and proteins, including tandemly repeated copies of rDNA for rRNA genes, RNA polymerase I (Pol I, one of the three RNA polymerases) that exclusively transcribes rDNA (Goodfellow and Zomerdijk, 2013) and factors involved in ribosome biogenesis, which is coupled to the transcription of rRNA genes. Malfunction in Pol I transcription of rRNA genes and abnormality in rDNA clusters are common features in cancer cells and human diseases (Hariharan and Sussman, 2014; Peltonen et al, 2014; Quin et al, 2014; van Sluis and McStay, 2014). …”

Section: Differences In Genome Organization Transcription Machinery mentioning

confidence: 99%

Nucleolus-like compartmentalization of the transcription machinery in fast-growing bacterial cells

Jin

Martín-Franco

Sun

et al. 2016

Critical Reviews in Biochemistry and Molecular Biology

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Overview. We have learned a great deal about RNA polymerase (RNA Pol), transcription factors, and the transcriptional regulation mechanisms in prokaryotes for specific genes, operons, or transcriptomes. However, we have only begun to understand how the transcription machinery is 3-dimensionally (3D) organized into bacterial chromosome territories to orchestrate the transcription process and to maintain harmony with the replication machinery in the cell. Much progress has been made recently in our understanding of the spatial organization of the transcription machinery in fast-growing Escherichia coli cells using state-of-the-art superresolution imaging techniques. Co-imaging of RNA polymerase (RNA Pol) with DNA and transcription elongation factors involved in ribosomal RNA (rRNA) synthesis and ribosome biogenesis has revealed similarities between bacteria and eukaryotes in the spatial organization of the transcription machinery for growth genes, most of which are rRNA genes. Evidence supports the notion that RNA Pol molecules are concentrated, forming foci at the clustering of rRNA operons resembling the eukaryotic nucleolus. RNA Pol foci are proposed to be active transcription factories for both rRNA genes expression and ribosome biogenesis to support maximal growth in optimal growing conditions. Thus, in fast-growing bacterial cells, RNA Pol foci mimic eukaryotic Pol I activity, and transcription factories resemble nucleolus-like compartmentation. In addition, the transcription and replication machineries are mostly segregated in space to avoid the conflict between the two major cellular functions in fast-growing cells.

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Section: Differences In Genome Organization Transcription Machinery mentioning

confidence: 99%

Nucleolus-like compartmentalization of the transcription machinery in fast-growing bacterial cells

Jin

Martín-Franco

Sun

et al. 2016

Critical Reviews in Biochemistry and Molecular Biology

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“…Na slici 1 apeks krivulje učestalosti AgNOR publikacija, u kojima se prvenstveno radi o tumorskoj patologiji, ukazuje na nagli porast interesa za funkciju ribosomalnih gena u onkogenezi i uvod je u istraživanje jezgrice dinamičkim molekularnim metodama na ulazu u 21. stoljeće kada dolazi do promjene definicije jezgrice. Povezivanjem oblika, strukture i funkcije AgNOR metoda ukazuje na razvoj znanstvene misli, te daje uvid u povezanost jezgrice s patološkim stanjima koja su danas opisana molekularnim metodama [76][77][78][79][80]111,[122][123][124][125][126][127][128][129][130][131][132] . Time patologija, molekularna biologija i biotehnologija dobivaju zajednički cilj istraživanja: jezgricu u bolesti, što je vidljivo i ovdje u slici 1 i 2, a u čemu među prvima sudjeluju znanstvenici Medicinskog fakulteta u Rijeci 132 .…”

Section: Grupa Za Agnor I Rezultati S Apeksomunclassified

Descriptive and functional definition of nucleolus – a pathway to cancer therapy

et al. 2016

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Sažetak. Očekuje se da moderna terapija tumora djeluje ciljano i sveobuhvatno. U novim kliničkim ispitivanjima terapije raka primjenjuju se mali molekularni inhibitori transkripcije ribosomalnih gena i aktivatori apoptoze. Model terapije prikazan ovdje je aktivacija supresora tumora koji djeluju u domeni jezgrice. Stanice tumora pokazuju poremećaj regulacije proteina i mutaciju P53 gena koji suprimira rast. Razvoj bolesti definira terapiju. Moderna se definicija bolesti temelji na etiopatogenezi staničnog stresa u kojem sudjeluju brojne organele, uključujući jezgricu. Jezgra i jezgrica su mikroskopski oblici. Ovaj prikaz daje sažet opis onoga što se vidi kada se kaže "jezgrica". Nadalje su opisani kiseli nehistonski proteini koji se okupljaju oko transkripcijskog ustroja RNK polimeraze I te je istaknut značaj njihove vizualizacije za promjenu definicije jezgrice. Osim što je tjelešce u nukleoplazmi i subnuklearna organela, jezgrica se može vizualizirati pomoću njezinih funkcionalnih struktura -AgNOR-a. AgNOR proteini imaju ulogu u nukleolarnom stresu. Svrha ovoga teksta je raspraviti nukleolarni stres.Ključne riječi: biološki stres; bolest; karcinogeneza; stanična jezgrica; terapija Abstract. Modern tumour therapy should be target specific and comprehensive. Recent clinical trials test small molecular inhibitors of transcription of ribosomal genes and activators of apoptosis. We treatise on models of activation of the suppressors of tumour growth acting in the nucleolar domain. Tumour cells demonstrate a disordered protein regulation and mutation of P53 gene which codes for a suppressor of growth. Therapy is guided by pathogenesis. Modern disease definition is based on etiopathogenesis of cell stress, wherein participate numerous organelles, including the nucleolus. Nucleus and nucleolus are forms seen on light microscopy. This presentation focuses on the description of the visible correlate of the notion of "nucleolus". Further to this, acid non-histone proteins which gather around the transcriptional machinery of RNA polymerase I are described, and the significance of their visualisation towards the alteration of the definition of nucleolus is pointed out. Besides being a particle within the nucleoplasm and a subnuclear organelle, the nucleolus is visualized through its functional structures -the AgNORs. The AgNOR proteins have a role in nucleolar stress. The aim of this article is to discuss the nucleolar stress.

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“…[20] demonstrated that overexpression of nucleostemin in human adult CPCs antagonizes their senescence by decreasing the number of senescent and multinucleated cells, and by restoring a youthful cell morphology. Nucleostemin is a nucleolar protein activated downstream of Pim-1 and is known to regulate ribosomal biogenesis, proliferation and growth of stem cells [21]. Given their efficacy in antagonizing hCPC senescence, Pim-1 and nucleostemin constitute promising candidates for future interventional approaches to restore reparative potential in the aged failing heart.…”

Section: Strategies To Rejuvenate the Senescent Heartmentioning

confidence: 99%

Rejuvenating the senescent heart

Nguyen

Sussman

2015

Current Opinion in Cardiology

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Purpose of review The purpose of this review is to provide an update on the cardiac stem cell field with an emphasis on aging and to suggest some relevant strategies directed toward rejuvenation of the senescent heart. Recent findings Stem cells were long considered as a fountain of youth and were assumed to be equipped against any form of aging effect. However, it is now clear that stem cells suffer the consequences of aging as well. With the discovery that cardiac stem cells reside in the heart comes the question whether these cells are also impaired upon aging. As cardiac stem cell properties are also altered with age, autologous stem cell-based therapy to treat heart failure will benefit from new improved strategies. Summary With the goal to improve stem cell properties that are impaired upon aging, some strategies are highlighted. Genetic modification of adult human cardiac progenitor cells prior to autologous stem cell-based therapy, delivery of the next generation of stem cells such as CardioChimeras and CardioClusters, and improvement of the myocardial environment with rejuvenating factors constitute some of the possibilities and are discussed in more detail in this review.

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Stressing on the nucleolus in cardiovascular disease

Cited by 38 publications

References 64 publications

Nucleolus-like compartmentalization of the transcription machinery in fast-growing bacterial cells

Nucleolus-like compartmentalization of the transcription machinery in fast-growing bacterial cells

Descriptive and functional definition of nucleolus – a pathway to cancer therapy

Rejuvenating the senescent heart

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