Related Experiment Videos
Nuclear factor I interferes with transformation induced by nuclear oncogenes
E R Schuur1, U Kruse, J S Iacovoni
1Department of Molecular and Experimental Medicine, Scripps Research Institute, La Jolla, California 92037, USA.
Cell Growth & Differentiation : the Molecular Biology Journal of the American Association for Cancer Research
|March 1, 1995
Summary
Overexpressing nuclear factor I (NFI) proteins in chicken cells altered their shape and adherence. These cells resisted transformation by nuclear oncogenes but remained susceptible to cytoplasmic oncogenes.
Area of Science:
- Molecular Biology
- Cell Biology
- Oncology
Background:
- Nuclear Factor I (NFI) proteins, encoded by four genes (NFI-A, NFI-B, NFI-C, NFI-X), produce multiple isoforms via alternative splicing.
- NFI proteins interact with transcription factors like AP-1 and Myc to regulate gene expression.
Purpose of the Study:
- To investigate the growth-regulatory potential of NFI proteins.
- To determine the effects of NFI overexpression on chicken embryo fibroblasts (CEF) and their susceptibility to oncogenic transformation.
Main Methods:
- Overexpression of chicken NFI cDNAs (-A, -B, -C, -X) in CEF.
- Assessment of cell morphology, adherence, and growth properties.
- Challenging morphologically altered CEF with oncogenic retroviruses encoding nuclear and cytoplasmic oncogenes.
- Analysis of NFI-A1 protein's effect on Jun protein transactivation.
Main Results:
- NFI overexpression did not induce oncogenic transformation but caused significant morphological changes (flattening, increased adherence) in CEF.
- Morphologically altered CEF exhibited resistance to transformation by nuclear oncogenes (jun, fos, myc) but remained susceptible to cytoplasmic oncogenes (src, ras).
- NFI-A1 protein modulated Jun protein transactivation in a promoter-dependent manner, with the transactivation domain being crucial for observed effects.
Conclusions:
- The transactivation domain of NFI proteins is essential for inducing morphological changes and altering oncogene susceptibility.
- NFI proteins play a role in regulating cellular responses to different classes of oncogenes, highlighting a dichotomy between nuclear and cytoplasmic oncogene activities.