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Structure and function of p21 ras proteins.
T Y Shih1, S Hattori, D J Clanton
1Division of Cancer Etiology, National Cancer Institute, Frederick, MD 21701.
Summary
Cancer involves faulty cell growth control. Ras proteins, similar to G-proteins, are key to understanding cell growth signals and cancer development. Their on/off switch function offers new intervention strategies.
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- Cancer arises from uncontrolled cellular growth.
- Ras genes encode p21 proteins involved in cell growth signaling.
- p21 proteins share similarities with other guanine nucleotide-binding proteins (G-proteins).
Purpose of the Study:
- To elucidate the structure and function of p21 ras proteins.
- To understand the role of p21 proteins in cellular signal transduction.
- To explore the mechanism of proto-oncogene activation.
Main Methods:
- Gene cloning and sequencing
- Protein overproduction and engineering
- Biochemical characterization and X-ray crystallography
- Site-directed mutagenesis and immunochemical probes
Main Results:
- p21 ras proteins possess a membrane-binding domain and conserved regions.
- Guanosine diphosphate (GDP) binding sites are conserved between p21 and elongation factor Tu (EF-Tu).
- Guanosine triphosphate (GTP) binding is essential for p21 ras cellular function.
Conclusions:
- Ras gene 'on/off' switch function provides insight into proto-oncogene activation.
- Understanding p21 ras function may lead to novel cancer intervention strategies.
- Further research into p21 target molecules is warranted.