Direct interaction of Gas41 and Myc encoded by amplified genes in nervous system tumours.

Abstract

In order to understand better the role of the human Tip60 complex component Gas41, we analysed its expression levels in brain tumours and searched for possible interactors. Two-hybrid screening of a human foetal brain library allowed identification of some molecular interactors of Gas41. Among them we found n-Myc transcription factor. The interaction between Gas41 and n-Myc was validated by pull-down experiments. We showed that Gas41 is able to bind both n-Myc and c-Myc proteins, and that the levels of expression of Gas41 and Myc proteins were similar to each other in such brain tumors as neuroblastomas and glioblastomas. Finally, in order to identify which region of Gas41 is involved in the interaction with Myc proteins, we analysed the ability of Gas41 to substitute for its orthologue Yaf9 in yeast; we showed that the N-terminal portions of the two proteins, containing the YEATS domains, are interchangeable, while the C-terminal portions are species-specific. In fact we found that Gas41 C-terminal portion is required for Myc protein interaction in human.

• Authors: Eugenia Piccinni, Anna Chelstowska, Jakub Hanus, Piotr Widlak, Simona Loreti, Ada Maria Tata, Gabriella Augusti-Tocco, Michele Maria Bianchi, Rodolfo Negri
• Journal: Acta biochimica Polonica (Acta Biochim Pol) Vol. 58 Issue 4 Pg. 529-34 ( 2011) ISSN: 1734-154X [Electronic] Poland
• PMID: 22068108 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• MYC protein, human
• Proto-Oncogene Proteins c-myc
• Recombinant Fusion Proteins
• Saccharomyces cerevisiae Proteins
• Transcription Factors
• YAF9 protein, S cerevisiae
• YEATS4 protein, human
• Histone Acetyltransferases

Topics

• Brain (cytology, metabolism)
• Brain Neoplasms (genetics, metabolism, pathology)
• Cell Line, Tumor
• Cloning, Molecular
• Fetus (cytology, metabolism)
• Gene Expression Profiling
• Gene Expression Regulation, Neoplastic
• Gene Library
• Genes, Neoplasm
• Genetic Vectors (genetics, metabolism)
• Glioblastoma (genetics, metabolism, pathology)
• Histone Acetyltransferases (genetics, metabolism)
• Humans
• Neuroblastoma (genetics, metabolism, pathology)
• Plasmids (genetics, metabolism)
• Protein Interaction Domains and Motifs
• Protein Interaction Mapping
• Proto-Oncogene Proteins c-myc (genetics, metabolism)
• Recombinant Fusion Proteins (genetics, metabolism)
• Saccharomyces cerevisiae (genetics, metabolism)
• Saccharomyces cerevisiae Proteins (genetics, metabolism)
• Silver Staining
• Species Specificity
• Transcription Factors (genetics, metabolism)
• Two-Hybrid System Techniques