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Positive regulation of cdc2 gene activity by protein phosphatase type 2A
V L Jaramillo-Babb1, J L Sugarmans, R Scavetta
1Department of Molecular Microbiology and Immunology, University of California, Los Angeles 90033-1034, USA.
Abstract:
Several lines of evidence indicate that serine/threonine protein phosphatases may act as negative regulators of cellular growth. For example, treatment of cells with the tumor-promoter okadaic acid, an inhibitor of certain types of these phosphatases, resulted in the increased expression of several proto-oncogenes, indicating a negative role of the respective phosphatases in gene regulation. However, it was puzzling to find that okadaic acid-treated cells, even in the presence of highly expressed proto-oncogenes, did not proliferate, but were arrested at certain points of the cell cycle. To further analyze this discrepancy, we investigated the involvement of protein phosphatases in the control of other cell cycle regulatory genes, such as cdc2 which encodes an essential cell cycle regulatory kinase. We found that cdc2 gene expression was blocked by okadaic acid, but stimulated by protein phosphatase 2A. Protein phosphatase 2A is shown to be a positive regulator of cdc2 gene activity and to be required for cdc2 expression. Thus, our findings identify protein phosphatase 2A as a positive regulator of a major cell cycle regulatory gene and therefore suggest a stimulatory role of this enzyme in this aspect of cellular growth control.
Insights
Protein phosphatase 2A positively regulates the cdc2 gene, a key cell cycle regulator. This enzyme is crucial for cell proliferation, contradicting previous assumptions about phosphatases inhibiting growth.
Area of Science:
- Molecular Biology
- Cell Biology
- Biochemistry
Background:
- Serine/threonine protein phosphatases are implicated as negative regulators of cellular growth.
- Inhibitors like okadaic acid increase proto-oncogene expression but cause cell cycle arrest, a puzzling observation.
- The role of phosphatases in cell cycle gene regulation requires further investigation.
Purpose of the Study:
- To investigate the role of protein phosphatases in regulating cell cycle genes, specifically cdc2.
- To clarify the discrepancy between proto-oncogene expression and cell proliferation observed with okadaic acid treatment.
Main Methods:
- Treatment of cells with okadaic acid, a phosphatase inhibitor.
- Analysis of cdc2 gene expression.
- Investigating the effect of protein phosphatase 2A on cdc2 gene activity.
Main Results:
- Okadaic acid treatment blocked cdc2 gene expression.
- Protein phosphatase 2A was found to stimulate cdc2 gene expression.
- Protein phosphatase 2A is essential for cdc2 expression and acts as a positive regulator.
Conclusions:
- Protein phosphatase 2A is a positive regulator of the cdc2 gene, a critical cell cycle control element.
- This enzyme plays a stimulatory role in cellular growth by promoting cell cycle progression.