Search

Your search keyword '"Montanaro L"' showing total 835 results
Start Over Author "Montanaro L"
835 results on '"Montanaro L"'

1. The emerging role of RNA polymerase I transcription machinery in human malignancy: a clinical perspective

Author

Montanaro L, Treré D, and Derenzini M

Subjects
Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Lorenzo Montanaro, Davide Treré, Massimo Derenzini Department of Experimental, Diagnostic and Specialty Medicine, Alma Mater Studiorum, University of Bologna, Bologna, Italy Abstract: Ribosome biogenesis – the complex and highly coordinated cellular process leading to the production of ribosomes – is strictly dependent on the activity of RNA polymerase I (Pol I) transcriptional machinery. Pol I activity is continually increased in proliferating cells to sustain the increased demand for ribosome production and protein synthesis, which are necessary for appropriate cell growth and division. The integrity of the process of ribosome biogenesis represents an important sensor of cellular stress: when this process is altered, a tumor suppressor response is triggered, which leads to proliferative arrest. The present review focuses on the possible implications of Pol I targeting in the treatment of human malignancies. Keywords: RNA polymerase I inhibitors, ribosome biogenesis, cell cycle control, cancer, Pol I

Published
2013

14. Ribosomal protein gene RPL9 variants can differentially impair ribosome function and cellular metabolism

Author

Lezzerini, M., Penzo, M., O'Donohue, M.F., Vieira, C. Marques Dos San, Saby, M., Elfrink, H.L., Diets, I.J., Hesse, A.M., Coute, Y., Gastou, M., Nin-Velez, A., Nikkels, P.G., Olson, A.N., Zonneveld-Huijssoon, E., Jongmans, M.C.J., Zhang, G., Weeghel, M. van, Houtkooper, R.H., Wlodarski, M.W., Kuiper, R.P, Bierings, M.B., Bosch, J, Leblanc, T., Montanaro, L., Dinman, J.D., Costa, L., Gleizes, P.E., Macinnes, A.W., Lezzerini, M., Penzo, M., O'Donohue, M.F., Vieira, C. Marques Dos San, Saby, M., Elfrink, H.L., Diets, I.J., Hesse, A.M., Coute, Y., Gastou, M., Nin-Velez, A., Nikkels, P.G., Olson, A.N., Zonneveld-Huijssoon, E., Jongmans, M.C.J., Zhang, G., Weeghel, M. van, Houtkooper, R.H., Wlodarski, M.W., Kuiper, R.P, Bierings, M.B., Bosch, J, Leblanc, T., Montanaro, L., Dinman, J.D., Costa, L., Gleizes, P.E., and Macinnes, A.W.

Abstract

Contains fulltext : 218593.pdf (publisher's version ) (Open Access), Variants in ribosomal protein (RP) genes drive Diamond-Blackfan anemia (DBA), a bone marrow failure syndrome that can also predispose individuals to cancer. Inherited and sporadic RP gene variants are also linked to a variety of phenotypes, including malignancy, in individuals with no anemia. Here we report an individual diagnosed with DBA carrying a variant in the 5'UTR of RPL9 (uL6). Additionally, we report two individuals from a family with multiple cancer incidences carrying a RPL9 missense variant. Analysis of cells from these individuals reveals that despite the variants both driving pre-rRNA processing defects and 80S monosome reduction, the downstream effects are remarkably different. Cells carrying the 5'UTR variant stabilize TP53 and impair the growth and differentiation of erythroid cells. In contrast, ribosomes incorporating the missense variant erroneously read through UAG and UGA stop codons of mRNAs. Metabolic profiles of cells carrying the 5'UTR variant reveal an increased metabolism of amino acids and a switch from glycolysis to gluconeogenesis while those of cells carrying the missense variant reveal a depletion of nucleotide pools. These findings indicate that variants in the same RP gene can drive similar ribosome biogenesis defects yet still have markedly different downstream consequences and clinical impacts.

Published
2020

15. DKC1 Overexpression Induces a More Aggressive Cellular Behavior and Increases Intrinsic Ribosomal Activity in Immortalized Mammary Gland Cells

Author

Guerrieri, AN, Zacchini, F, Onofrillo, C, Di Viggiano, S, Penzo, M, Ansuini, A, Gandin, I, Nobe, Y, Taoka, M, Isobe, T, Trere, D, Montanaro, L, Guerrieri, AN, Zacchini, F, Onofrillo, C, Di Viggiano, S, Penzo, M, Ansuini, A, Gandin, I, Nobe, Y, Taoka, M, Isobe, T, Trere, D, and Montanaro, L

Abstract

Dyskerin is a nucleolar protein involved in the small nucleolar RNA (snoRNA)-guided pseudouridylation of specific uridines on ribosomal RNA (rRNA), and in the stabilization of the telomerase RNA component (hTR). Loss of function mutations in DKC1 causes X-linked dyskeratosis congenita, which is characterized by a failure of proliferating tissues and increased susceptibility to cancer. However, several tumors show dyskerin overexpression. We observed that patients with primary breast cancers with high dyskerin levels are more frequently characterized by shorter survival rates and positive lymph node status than those with tumors with a lower dyskerin expression. To functionally characterize the effects of high dyskerin expression, we generated stably overexpressing DKC1 models finding that increased dyskerin levels conferred a more aggressive cellular phenotype in untransformed immortalized MCF10A cells. Contextually, DKC1 overexpression led to an upregulation of some snoRNAs, including SNORA67 and a significantly increased U1445 modification on 18S rRNA, the known target of SNORA67. Lastly, we found that dyskerin overexpression strongly enhanced the synthetic activity of ribosomes increasing translational efficiency in MCF10A. Altogether, our results indicate that dyskerin may sustain the neoplastic phenotype from an early stage in breast cancer endowing ribosomes with an augmented translation efficiency.

Published
2020

18. Enhanced telomere shortening in transformed lymphoblasts from patients with X linked dyskeratosis

Author

Montanaro, L, Tazzari, PL, and Derenzini, M

Subjects
Cell death -- Genetic aspects -- Physiological aspects -- Health aspects -- Research, Clinical pathology -- Research -- Physiological aspects -- Health aspects, Gene expression -- Physiological aspects -- Research -- Genetic aspects -- Health aspects, Epithelial cells -- Abnormalities, Lymphatics -- Physiological aspects -- Genetic aspects -- Health aspects -- Research, Cancer cells -- Genetic aspects -- Physiological aspects -- Research -- Health aspects, Proteins -- Physiological aspects -- Genetic aspects -- Health aspects -- Research, Health, Care and treatment, Physiological aspects, Genetic aspects, Research, Health aspects
Abstract

Aim: Dyskeratosis congenita (DC) is characterised by the failure of those tissues that are rapidly dividing in the adult, particularly the skin, mucosae, and haemopoietic system. The X linked form [...]

Published
2003

Catalog

Books, media, physical & digital resources
See catalog results