http://www.cnr.it/ontology/cnr/individuo/prodotto/ID21129
H4(D10S170), a gene frequently rearranged with RET in papillary thyroid carcinomas: functional characterization. (Articolo in rivista)
- Type
- Label
- H4(D10S170), a gene frequently rearranged with RET in papillary thyroid carcinomas: functional characterization. (Articolo in rivista) (literal)
- Anno
- 2004-01-01T00:00:00+01:00 (literal)
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- Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
- Celetti A; Cerrato A; Merolla F; Vitagliano D; Vecchio G; Grieco M. (literal)
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- Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroVolume
- Rivista
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- ISI Web of Science (WOS) (literal)
- Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni
- Istituto di Endocrinologia ed Oncologia Sperimentale del CNR c/o Dipartimento di Biologia e Patologia Cellulare e Molecolare, University 'Federico II', Naples, Italy; and Dipartimento di Medicina Sperimentale e Clinica, Universita` 'Magna Graecia', via T. Campanella 115, Policlinico Materdomini, Catanzaro, CZ 88100, Italy (literal)
- Titolo
- H4(D10S170), a gene frequently rearranged with RET in papillary thyroid carcinomas: functional characterization. (literal)
- Abstract
- Human thyroid papillary carcinomas are characterized by rearrangements of the RET protooncogene with a number of heterologous genes, which generate the RET/papillary thyroidcarcinoma(PTC)oncogenes.Oneofthemost frequent variants of these recombination events is the fusion of the intracellular kinase-encoding domain of RET to the first 101 amino acids of a gene named H4(D10S170).WehavecharacterizedtheH4(D10S170) gene product, showing that it is a ubiquitously expressed 55KDa nuclear and cytosolic protein that is phosphory- latedfollowingserumstimulation.Thisphosphorylation was found to depend on mitogen-activated protein kinase(MAPK)Erk1/2activityandtobeassociated totherelocationofH4(D10S170)fromthenucleusto the cytosol. Overexpression of the H4(D10S170) gene was able to induce apoptosis of thyroid follicular epithelial cells; conversely a carboxy-terminal truncated H4(D10S170) mutant H4(1-101), corresponding to the portion included in the RET/PTC1 oncoprotein, behaved as dominant negative on the proapoptotic function and nuclear localization of H4(D10S170). Furthermore, con- ditional expression of the H4(D10S170)-dominant nega- tive truncated mutant protected cells from stress-induced apoptosis. The substitution of serine 244 with alanine abrogated the apoptotic function of H4(D10S170). These data suggest that loss of the H4(D10S170) gene function might have a role in thyroid carcinogenesis by impairing apoptosis. (literal)
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