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Constitutive expression of the interferon-inducible protein p202 in NIH 3T3 cells affects cell cycle progression
D Lembo1, A Angeretti, S Benefazio
1Department of Hygiene and Microbiology, University of Torino, Italy.
Abstract:
p202 is a protein expressed in murine cells after Interferon treatment. Although the function of p202 is still basically unknown, its ability to bind the hypophosphorylated form of the retinoblastoma protein pRb suggests a possible role in the control of cell proliferation. To investigate the role of p202 we have generated several cell clones of NIH 3T3 fibroblasts that constitutively express p202. Here we show that proliferation of quiescent cells on stimulation by serum addition is strongly inhibited by constitutive p202 expression. Moreover, when growth arrested cells are stimulated to proliferate, expression of p202 inhibits G0/G1 progression into the S phase and the cells accumulate with a DNA content that is equivalent to cells arrested in the G0/G1 phase of the cell cycle. Taken together, these studies suggest that p202 may play a negative role in growth regulation.
Insights
The protein p202 inhibits cell proliferation by blocking cell cycle progression. Constitutive p202 expression in fibroblasts prevents entry into the S phase, suggesting a negative role in growth regulation.
Area of Science:
- Molecular Biology
- Cell Biology
- Biochemistry
Background:
- p202 is a protein induced by Interferon in murine cells.
- Its function is largely unknown, but it binds hypophosphorylated retinoblastoma protein (pRb).
- This interaction suggests a role in cell proliferation control.
Purpose of the Study:
- To investigate the role of p202 in cell growth regulation.
- To determine the effect of constitutive p202 expression on fibroblast proliferation.
Main Methods:
- Generation of NIH 3T3 fibroblast cell clones expressing p202.
- Analysis of cell cycle progression in quiescent and growth-stimulated cells.
- Flow cytometry to assess DNA content and cell cycle phase distribution.
Main Results:
- Constitutive p202 expression strongly inhibited the proliferation of quiescent NIH 3T3 cells upon serum stimulation.
- p202 expression blocked the progression of growth-arrested cells from G0/G1 to S phase.
- Cells expressing p202 accumulated with G0/G1 DNA content.
Conclusions:
- p202 plays a negative regulatory role in cell growth.
- p202 expression can arrest cells in the G0/G1 phase of the cell cycle.
- Further research into p202's mechanism in growth control is warranted.