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Oncogene jun encodes a sequence-specific trans-activator similar to AP-1
P Angel1, E A Allegretto, S T Okino
1Department of Pharmacology M-036, School of Medicine, University of California, San Diego, La Jolla 92093.
Abstract:
Proto-oncogenes encode proteins with three main sites of action: the cell-surface membrane, the cytoplasm and the nucleus. Although the exact biochemical function of most proto-oncogene products is not understood, several of them are known to be involved in signal transduction. A role in gene regulation through DNA binding has been suggested for a recently isolated member of the group of oncogenes acting at the nucleus, v-jun. The C-terminus of the putative v-jun-encoded protein is similar in sequence to the C-terminus of the yeast transcriptional activator GCN4 (refs 8, 9), which forms its minimal DNA-binding domain. GCN4 binds to specific sites whose consensus sequence is highly similar to the recognition sequence of the mammalian transcriptional activator AP-1 (refs 12, 13). Like GCN4, AP-1 binds to promoter elements of specific genes and activates their transcription. Because of the similarity between the recognition sites for GCN4 and AP-1, we examined the possibility that AP-1 could be the product of the c-jun proto-oncogene. The experimental results reported here indicate that the JUN oncoprotein is a sequence-specific transcriptional activator similar to AP-1.
Insights
Proto-oncogenes regulate cell functions. The JUN oncoprotein acts as a sequence-specific transcriptional activator, similar to AP-1, playing a key role in gene regulation.
Area of Science:
- Molecular Biology
- Cell Biology
- Genetics
Background:
- Proto-oncogenes encode proteins involved in cellular signal transduction.
- v-jun, a nuclear oncogene, is implicated in gene regulation via DNA binding.
- The yeast transcriptional activator GCN4 shares sequence similarity with v-jun and binds DNA.
Purpose of the Study:
- To investigate the functional relationship between the c-jun proto-oncogene and the transcription factor AP-1.
- To determine if the JUN oncoprotein functions as a sequence-specific transcriptional activator.
Main Methods:
- Sequence homology analysis between v-jun and GCN4.
- Comparison of DNA recognition sites for GCN4 and AP-1.
- Experimental validation of JUN oncoprotein's transcriptional activity.
Main Results:
- The C-terminus of v-jun shares sequence similarity with the DNA-binding domain of GCN4.
- GCN4 and AP-1 recognize similar DNA consensus sequences.
- Experimental data indicate that the JUN oncoprotein is a sequence-specific transcriptional activator, functionally similar to AP-1.
Conclusions:
- The JUN oncoprotein is a sequence-specific transcriptional activator.
- JUN oncoprotein likely plays a role in gene regulation analogous to AP-1.
- This finding elucidates the function of a proto-oncogene product in transcriptional regulation.