A topogenic role for the oncogenic N-terminus of TLS: nucleolar localization when transcription is inhibited
| Autor: | Helene Zinszner, David Immanuel, David Ron, Yin Yin, Feng-Xia Liang |
|---|---|
| Rok vydání: | 1997 |
| Předmět: |
Cancer Research
Amanitins Transcription Genetic Immunoelectron microscopy RNA-binding protein Biology Heterogeneous ribonucleoprotein particle Transfection Heterogeneous-Nuclear Ribonucleoproteins Cell Line Mice Cricetinae Genetics medicine Tumor Cells Cultured Animals Humans RNA Messenger Molecular Biology Ribonucleoprotein Fibrillarin 3T3 Cells Oncogenes Interchromatin granule Recombinant Proteins Cell biology Neoplasm Proteins Cell nucleus medicine.anatomical_structure Biochemistry Ribonucleoproteins COS Cells Dactinomycin RNA-Binding Protein FUS RNA-Binding Protein EWS Cell Division Cell Nucleolus Dichlororibofuranosylbenzimidazole HeLa Cells |
| Zdroj: | Oncogene. 14(4) |
| ISSN: | 0950-9232 |
| Popis: | TLS (FUS) and the related gene EWS encode the N-terminal portion of many fusion oncoproteins involved in human sarcomas and leukemia. TLS is an RNA-binding nuclear protein that is identical to hnRNP P2 and may be implicated in mRNA metabolism. When RNA polymerase II is inhibited, TLS immunostaining in the nucleus is dramatically altered, from its normal diffuse nucleoplasmic pattern to accumulation in dense nuclease-resistant aggregates. Co-immunostaining with antibodies to fibrillarin or p80 coilin and immunoelectron microscopy revealed that the TLS aggregates are associated with the nucleolus and are distinct from other known structures such as the coiled body or the interchromatin granule. Injection of cells with an oligodeoxynucleotide that disrupts splicing does not result in redistribution of TLS, indicating that the event is specific to inhibition of transcription. Oncoproteins that contain the N-terminal domain from either TLS, EWS or their Drosophila homologue, SARFH (CAZ), are also targeted to the same structure. These findings suggest a correlation between the topogenic and transforming activities of TLS and EWS N-termini and imply the existence of cellular targets that are shared by the germ-line encoded proteins and their oncogenic derivatives. |
| Databáze: | OpenAIRE |
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