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Preparation of Cell-lines for Conditional Knockdown of Gene Expression and Measurement of the Knockdown Effects on E4orf4-Induced Cell Death
Published on: October 21, 2012
E2F-1 functions in mice to promote apoptosis and suppress proliferation
1Division of Neuroscience, Children's Hospital, Boston, Massacusetts, O2115,P5USA.
Abstract:
Members of the E2F transcription factor family (E2F-1-E2F-5) are believed to be critical positive regulators of cell cycle progression in eukaryotes although the in vivo functions of the individual E2Fs have not been elucidated. Mice were generated that lack E2F-1 and, surprisingly, these mice develop and reproduce normally. However, E2F-1-/- mice exhibit a defect in T lymphocyte development leading to an excess of mature T cells due to a maturation stage-specific defect in thymocyte apoptosis. As E2F-1-/- mice age they exhibit a second phenotype marked by aberrant cell proliferation. These findings suggest that while certain members of the E2F family may positively regulate cell cycle progression, E2F-1 functions to regulate apoptosis and to suppress cell proliferation.
Insights
Mice lacking E2F-1 developed normally but showed defects in T lymphocyte development and thymocyte apoptosis. Aged E2F-1 knockout mice also displayed aberrant cell proliferation, indicating E2F-1 regulates apoptosis and suppresses proliferation.
Area of Science:
- Molecular Biology
- Immunology
- Developmental Biology
Background:
- E2F transcription factors (E2F-1-E2F-5) are implicated as positive regulators of eukaryotic cell cycle progression.
- The specific in vivo functions of individual E2F family members remain largely unelucidated.
Purpose of the Study:
- To investigate the in vivo function of the E2F-1 transcription factor.
- To elucidate the role of E2F-1 in T lymphocyte development and cell proliferation.
Main Methods:
- Generation and analysis of E2F-1 knockout (E2F-1-/-) mice.
- Assessment of T lymphocyte development, thymocyte apoptosis, and cell proliferation in E2F-1-/- mice.
Main Results:
- E2F-1-/- mice developed and reproduced normally, with no gross developmental abnormalities.
- A specific defect in T lymphocyte development was observed, characterized by an excess of mature T cells due to impaired thymocyte apoptosis at a particular maturation stage.
- Aged E2F-1-/- mice exhibited a secondary phenotype of aberrant cell proliferation.
Conclusions:
- E2F-1 plays a critical role in regulating apoptosis during T lymphocyte development.
- E2F-1 functions to suppress aberrant cell proliferation, particularly in aged individuals.
- These findings highlight a distinct role for E2F-1 in apoptosis regulation and proliferation control, separate from the cell cycle progression roles of other E2F family members.
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