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Mutual interactions between p53 and growth factors in cancer
J G Asschert1, E Vellenga, S De Jong
1Department of Internal Medicine, University Hospital Groningen, The Netherlands.
Abstract:
The function of p53 tumour suppressor protein is determined by various intrinsic properties of the protein. The effect of p53 DNA-binding, and protein-protein interactions are determined by the conformation of the protein. Thus, p53 fulfils its role in cell cycle control and the onset of apoptotic cell death, which is altered when the wild-type p53 (wt-p53) conformation is changed due to mutation. This review focuses on the communal interactions of wt- and mutant p53 (m-p53) with growth factors and shows that m-p53 affects different cell biological functions that determine the malignant behaviour of cells. P53, for instance, affects the response of cells to growth factors and growth factor-withdrawal. Furthermore, p53 is involved in the expression of several growth factor- and growth factor receptor genes. These data suggest that restoration of the wt-p53 phenotype in tumour cells with m-53 might not only affect cell cycle control and apoptotic mechanisms but could also reduce autocrine growth and restore sensitivity to physiological growth inhibitors.
Insights
Restoring wild-type p53 protein function in cancer cells can impact cell cycle and apoptosis. Mutant p53 affects growth factor interactions, influencing malignant cell behavior and potentially restoring normal growth regulation.
Area of Science:
- Molecular Biology
- Cancer Biology
- Biochemistry
Background:
- The p53 tumor suppressor protein's function is intrinsically linked to its conformation, affecting DNA binding and protein interactions.
- Wild-type p53 (wt-p53) is crucial for cell cycle control and apoptosis, processes disrupted by mutations leading to mutant p53 (m-p53).
Purpose of the Study:
- This review examines the interactions between wt-p53 and m-p53 with growth factors.
- To elucidate how m-p53 influences cellular functions that drive malignant progression.
Main Methods:
- Literature review focusing on p53 interactions with growth factors and receptors.
- Analysis of studies investigating the functional consequences of p53 mutations on cell biology.
Main Results:
- Mutant p53 significantly alters cellular responses to growth factors and growth factor withdrawal.
- p53 plays a role in regulating the expression of growth factor and growth factor receptor genes.
- m-p53 impacts various cellular functions, contributing to the malignant phenotype of cancer cells.
Conclusions:
- Restoring wt-p53 in tumors with m-p53 may restore cell cycle control and apoptosis.
- Restoration of wt-p53 could reduce tumor autocrine growth and re-sensitize cells to growth inhibitors.