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Transformation by the fos or jun oncogene does not increase AP-1 DNA-binding activity
K L Hawker1, A Pintzas, R F Hennigan
1Cancer Research Campaign Laboratories, Beatson Institute for Cancer Research, Bearsden, Glasgow, United Kingdom.
Journal of Virology
|September 1, 1993
Summary
Oncogene transformation by v-fos or v-jun does not alter AP-1 DNA-binding activity levels. However, v-jun transformation disrupts the normal cyclical regulation of AP-1 activity in response to serum stimulation.
Area of Science:
- Molecular Biology
- Oncology
- Cellular Regulation
Background:
- The transcription factor AP-1 is composed of proteins encoded by c-fos and c-jun proto-oncogenes.
- Oncogenic transformation can alter cellular regulatory pathways, including transcription factor activity.
Purpose of the Study:
- To investigate if v-fos or v-jun oncogene transformation affects AP-1 DNA-binding activity levels and regulation.
- To determine the role of AP-1 activity in oncogenic transformation by fos and jun.
Main Methods:
- Characterization of AP-1 DNA-binding activity in nuclear extracts.
- Comparison of transformed (v-fos, c-fos, v-jun) and normal (rat, chicken) fibroblasts.
- Analysis under various growth conditions, including serum stimulation.
Main Results:
- AP-1 DNA-binding activity levels were similar in proliferating transformed and normal cells, despite oncoprotein overexpression.
- Normal fibroblasts showed low basal AP-1 activity, increasing biphasically with serum stimulation.
- v-fos-transformed cells exhibited a similar cyclical pattern, while v-jun-transformed cells showed a lack of fluctuation in AP-1 activity upon serum stimulation.
Conclusions:
- Increased AP-1 DNA-binding is likely necessary but not sufficient for fos or jun-mediated transformation.
- The Jun component of the AP-1 complex may be responsible for regulating its activity in response to external stimuli like serum.